Co-reporter:Shao-Ru Wang, Yan-Yan Song, Lai Wei, Chao-Xing Liu, Bo-Shi Fu, Jia-Qi Wang, Xi-Ran Yang, Yi-Nong Liu, Si-Min Liu, Tian Tian, and Xiang Zhou
Journal of the American Chemical Society November 22, 2017 Volume 139(Issue 46) pp:16903-16903
Publication Date(Web):November 1, 2017
DOI:10.1021/jacs.7b09635
5-Formylcytosine (5fC) is identified as one of the key players in active DNA demethylation and also as an epigenetic mark in mammals, thus representing a novel attractive target to chemical intervention. The current study represents an attempt to develop a reversible 5fC-targeted intervention tool. A supramolecular aldehyde reactive probe was therefore introduced for selective conversion of the 5fC to 5fC-AD nucleotide. Using various methods, we demonstrate that cucurbit[7]uril (CB7) selectively targets the 5fC-AD nucleotide in DNA, however, the binding of CB7 to 5fC-AD does not affect the hydrogen bonding properties of natural nucleobases in duplex DNA. Importantly, CB7-driven host–guest chemistry has been applied for reversible intervention of a variety of 5fC-targeted biochemical reactions, including restriction endonuclease digestion, DNA polymerase elongation, and polymerase chain reaction. On the basis of the current study, the macrocyclic CB7 creates obstructions that, through steric hindrance, prevent the enzyme from binding to the substrate, whereas the CB7/5fC-AD host–guest interactions can be reversed by treatment with adamantanamine. Moreover, fragment- and site-specific identification of 5fC modification in DNA has been accomplished without sequence restrictions. These findings thus show promising potential of host–guest chemistry for DNA/RNA epigenetics.
Co-reporter:Tingting Hong;Fan Wu;Boshi Fu;Yushu Yuan;Jinglei Xu;Tianlu Wang
Chinese Journal of Chemistry 2017 Volume 35(Issue 6) pp:853-856
Publication Date(Web):2017/06/01
DOI:10.1002/cjoc.201600879
AbstractDNA methylation is an essential epigenetic modification, and found to be dynamically changed due to the observation of active DNA demethylation. During active demethylation, 5-methylcytosine (5mC) was oxidized stepwise by ten-eleven translocation (TET) enzymes into 5-hydroxymethylcytosine (5hmc), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Then, the subsequent excision of 5fC and 5caC combined with base excision repair further restored cytosine, which completes the demethylation process. Here, we report that 5-formylcytosine and 5-carboxylcytosine significantly reduce the activity of HhaI DNA methyltransferase to methylate target cytosines when present on the hemi-modified sequence of the complementary DNA. This finding demonstrates that 5fC and 5caC function as more than intermediates for active DNA demethylation.
Co-reporter:Shaoru Wang;Yanyan Song;Yafen Wang;Xin Li;Boshi Fu;Yinong Liu;Jiaqi Wang;Lai Wei;Tian Tian
Chemical Science (2010-Present) 2017 vol. 8(Issue 9) pp:6380-6388
Publication Date(Web):2017/08/21
DOI:10.1039/C7SC02340E
Natural nucleic acid bases can form Watson–Crick (WC) or Hoogsteen (HG) base pairs. Importantly, 8-oxo-2′-deoxyguanosine (8-oxo-dG) in DNA or 8-oxo-dG 5′-triphosphate (8-oxo-dGTP) favors a syn conformation because of the steric repulsion between O8 and O4′ of the deoxyribose ring. 8-oxo-dGTP can be incorporated into DNA opposite the templating adenine (A) using HG pairing as the dominant mechanism. Both RNA and DNA can be methylated at the N6 position of A to form N6-methyladenine (m6A). It has been found that certain viral infections may trigger an increase in the production of both 8-oxo-dGTP and m6A. The current study aims to systematically explore the effects of m6A methylation on HG base pairs and the consequent nucleotide incorporation. Our thermodynamic melting study shows that the m6A·8-oxo-dG is significantly less stable than the A·8-oxo-dG base pair in the paired region of a DNA duplex. Moreover, we have used pre-steady-state kinetics to examine the incorporation of 8-oxo-dGTP opposite m6A relative to A by a variety of reverse transcriptase (RT) enzymes and DNA polymerase (DNA pol) enzymes such as the human immunodeficiency virus type 1 (HIV-1) RT and human DNA pol β. The results demonstrate that all of these enzymes incorporate 8-oxo-dGTP less efficiently opposite m6A relative to A. Considering the steric bulk of the purine–purine pair between 8-oxo-dG and A, m6A methylation may affect the HG pairing to a great extent. Hence, it will be unfavorable to incorporate 8-oxo-dGTP into the growing strand opposite m6A. Moreover, the impeded incorporation of 8-oxo-dGTP opposite m6A has been extended to determine m6A at pre-defined positions in human rRNA. Our study may provide new insights into the roles of m6A in reducing the mutagenic potential of cellular 8-oxo-dGTP.
Co-reporter:Chaoxing Liu;Yafen Wang;Wei Yang;Fan Wu;Weiwu Zeng;Zonggui Chen;Jinguo Huang;Guangrong Zou;Xiong Zhang;Shaoru Wang;Xiaocheng Weng;Zhiguo Wu;Yu Zhou
Chemical Science (2010-Present) 2017 vol. 8(Issue 11) pp:7443-7447
Publication Date(Web):2017/10/23
DOI:10.1039/C7SC03685J
5-Formylcytosine (5fC), which plays an important role in epigenetic functions, has received widespread attention in many related fields. Here, we demonstrate a new design for both the fluorogenic switch-on detection and single-base resolution analysis of 5fC through selectively reacting a reagent with 5fC to yield an intramolecular cyclization nucleobase. The generated product, bearing a similar benzothiazole-iminocoumarin scaffold, is highly fluorescent and enables us to qualitatively and quantitatively detect 5fC moieties in γ-irradiated calf thymus DNA. Additionally, losing the exocyclic 4-amino group in 5fC causes the incorporation of dATP through base pairing with the generated nucleobase during polymerase extension, which helped us to analyze the 5fC sites in both single- and double-stranded oligonucleotides. Our Sanger and Illumina sequencing results show great potential in single-base resolution analysis of 5fC. It is hopeful that a similar design may be used for more detection targets.
Co-reporter:Chaoxing Liu;Yafen Wang;Xiong Zhang;Fan Wu;Wei Yang;Guangrong Zou;Qian Yao;Jiaqi Wang;Yuqi Chen;Shaoru Wang
Chemical Science (2010-Present) 2017 vol. 8(Issue 6) pp:4505-4510
Publication Date(Web):2017/05/30
DOI:10.1039/C7SC00637C
Recently, the detection of natural thymine modified 5-formyluracil has attracted widespread attention. Herein, we introduce a new insight into designing reagents for both the selective biotin enrichment and fluorogenic labelling of 5-formyluracil in DNA. Biotinylated o-phenylenediamine directly tethered to naphthalimide can switch on 5-formyluracil, under physiological conditions, which can then be used in cell imaging after exposure to γ-irradiation. In addition, its labelling property caused the polymerase extension to stop in the 5-formyluracil site, which gave us more information than the fluorescence did itself. The idea of detecting 5-formyluracil might be used in the synthesis of other modified diaminofluoresceins.
Co-reporter:Tingting Hong;Yushu Yuan;Tianlu Wang;Jingwei Ma;Qian Yao;Xiaoluan Hua;Yu Xia
Chemical Science (2010-Present) 2017 vol. 8(Issue 1) pp:200-205
Publication Date(Web):2016/12/19
DOI:10.1039/C6SC02271E
N6-methyladenine (6mA) is reported as a potential epigenetic marker in eukaryotic genomes. However, accurate identification of the location of 6mA in DNA remains a challenging task. Here, we show that Ag+ can selectively stabilize the A–C mismatch and efficiently promote primer extension. In contrast, the complex of 6mA–Ag+–C is instable and therefore cannot be recognized by DNA polymerases, resulting in the termination of primer extension. Based on this finding, we successfully identified and quantified 6mA at the single-base level through the analysis of gel bands of extended primers and fluorescence measurements combined with rolling circle amplification. The high selectivity and sensitivity of this strategy may provide a new platform for the efficient analysis of 6mA in DNA in the future.
Co-reporter:Yuqi Chen;Tingting Hong;Shaoru Wang;Jing Mo;Tian Tian
Chemical Society Reviews 2017 vol. 46(Issue 10) pp:2844-2872
Publication Date(Web):2017/05/22
DOI:10.1039/C6CS00599C
The epigenetic modification of nucleic acids represents one of the most significant areas of study in the field of nucleic acids because it makes gene regulation more complex and heredity more complicated, thus indicating its profound impact on aspects of heredity, growth, and diseases. The recent characterization of epigenetic modifications of DNA and RNA using chemical labelling strategies has promoted the discovery of these modifications, and the newly developed single-base or single-cell resolution mapping strategies have enabled large-scale epigenetic studies in eukaryotes. Due to these technological breakthroughs, several new epigenetic marks have been discovered that have greatly extended the scope and impact of epigenetic modifications in nucleic acids over the past few years. Because epigenetics is reversible and susceptible to environmental factors, it could potentially be a promising direction for clinical medicine research. In this review, we have comprehensively discussed how these epigenetic marks are involved in disease, including the pathogenesis, prevention, diagnosis and treatment of disease. These findings have revealed that the epigenetic modification of nucleic acids has considerable significance in various areas from methodology to clinical medicine and even in biomedical applications.
Co-reporter:Chaoxing Liu;Yuqi Chen;Yafen Wang;Fan Wu;Xiong Zhang;Wei Yang
Nano Research 2017 Volume 10( Issue 7) pp:2449-2458
Publication Date(Web):20 April 2017
DOI:10.1007/s12274-017-1445-2
The identification of hydroxylmethyl- and formylpyrimidines in genomic DNA was a landmark event in epigenetics. Numerous laboratories in related fields are investigating the biology of these and other nucleic acid modifications. However, limitations in the ability to detect and synthesize appropriate modifications are an impediment. Herein, we explored a remarkable development in the selective detection of 5-formyluracil in both single-stranded and double-stranded DNA under mild conditions. The “switch-on” specificity towards 5-formyluracil enabled a high signal-to-noise ratio in qualitatively and quantitatively detecting materials containing 5-formyluracil, which is not affected by the presence of abasic sites and 5-formylcytosine, the modified cytosine counterpart of 5-formyluracil. In summary, the innoxiousness, convenience, and cost-efficiency of the 5-formyluracil phosphoramidite synthetic routine would promote the understanding of the epigenetic role of this natural thymidine modification.
Co-reporter:Tian Tian; Yanyan Song; Jiaqi Wang; Boshi Fu; Zhiyong He; Xianqun Xu; Anling Li; Xin Zhou; Shaoru Wang
Journal of the American Chemical Society 2016 Volume 138(Issue 3) pp:955-961
Publication Date(Web):January 7, 2016
DOI:10.1021/jacs.5b11532
The fine control of enzyme activity is essential for the regulation of many important cellular and organismal functions. The light-regulation of proteins serves as an important method for the spatiotemporal control over the production and degradation of an enzyme product. This area is of intense interest for researchers. To the best of our knowledge, the use of small molecules as light-triggered molecular switches to reversibly control enzyme activity at the protein level has not yet been studied. In the present study, we demonstrate the light-controlled reversible regulation of the enzyme using a small-molecule-triggered switch, which is based on molecular recognition between an azobenzene derivative and telomere DNA. This molecule interconverts between the trans and cis states under alternate 365 nm UV and visible light irradiation, which consequently triggers the compaction and extension of telomere DNA. We further provide direct evidence for this structural switch using a circular dichroism study. Furthermore, our strategy has been successfully used to effectively control blood clotting in human plasma.
Co-reporter:Shaoru Wang, Jiaqi Wang, Xiaoe Zhang, Boshi Fu, Yanyan Song, Pei Ma, Kai Gu, Xin Zhou, Xiaolian Zhang, Tian Tian and Xiang Zhou
Chemical Science 2016 vol. 7(Issue 2) pp:1440-1446
Publication Date(Web):17 Nov 2015
DOI:10.1039/C5SC02902C
N
6-Methyladenine (m6A) is the most abundant internal modification on mammalian mRNA. Very recently, m6A has been reported as a potentially important ‘epigenetic’ mark in eukaryotes. Until now, site-specific detection of m6A is technically very challenging. Here, we first reveal that m6A significantly hinders DNA- and RNA-directed DNA synthesis. Systematic investigations of 5′-triphosphates of a variety of 5-substituted 2′-deoxyuridine analogs in primer extension have been performed. In the current study, a quantitative analysis of m6A in the RNA or DNA context has been achieved, using Bst DNA polymerase catalyzed primer extension. Molecular dynamics study predicted that m6A in template tends to enter into and be restrained in the MGR region of Bst DNA polymerase, reducing conformational flexibility of the DNA backbone. More importantly, a site-specific determination of m6A in human ribosomal RNA (rRNA) with high accuracy has been afforded. Through a cumulative analysis of methylation alterations, we first reveal that significantly cancer-related changes in human rRNA methylation were present in patients with hepatocellular carcinoma.
Co-reporter:Chen Xu, Jinjun Wu, Wenting Liu, Tingting Hong, Tianlu Wang, Xiaoe Zhang, Boshi Fu, Fan Wu, Zhiguo Wu and Xiang Zhou
Chemical Communications 2016 vol. 52(Issue 41) pp:6833-6836
Publication Date(Web):22 Apr 2016
DOI:10.1039/C6CC03138B
We present here a novel and efficient method for 5mC detection using a DNA strand exchange reaction (SER) strategy. This enzyme-free method needs no pre-treatment of target DNAs and can be adapted to most of the target duplexes under physiological conditions. The high sequence selectivity of this method can distinguish 5mC from normal cytosine in an accurate manner.
Co-reporter:Boshi Fu, Jinguo Huang, Yuqi Chen, Yafen Wang, Tianrui Xue, GuoHua Xu, Shaoru Wang and Xiang Zhou
Chemical Communications 2016 vol. 52(Issue 65) pp:10052-10055
Publication Date(Web):14 Jul 2016
DOI:10.1039/C6CC04866H
Herein, we report two distinct G-quadruplex conformations of the same G-rich oligonucleotide, regulated by a small molecule. This is the first report in which both right- and left-handed G-quadruplex conformations have been obtained from the same sequence. We discriminated these two distinct conformations and investigated their kinetics and thermodynamics.
Co-reporter:Shan Guo, Jiaquan Xu, Min Xie, Wei Huang, Erfeng Yuan, Ya Liu, Liping Fan, Shibo Cheng, Songmei Liu, Fubing Wang, Bifeng Yuan, Weiguo Dong, Xiaolian Zhang, Weihua Huang, and Xiang Zhou
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 25) pp:15917-15925
Publication Date(Web):June 6, 2016
DOI:10.1021/acsami.6b04002
Circulating tumor cells (CTCs) play a significant role in cancer diagnosis and personalized therapy, and it is still a significant challenge to efficiently capture and gently release CTCs from clinical samples for downstream manipulation and molecular analysis. Many CTC devices incorporating various nanostructures have been developed for CTC isolation with sufficient capture efficiency, however, fabricating such nanostructured substrates often requires elaborate design and complicated procedures. Here we fabricate a degradable zinc-phosphate-based hierarchical nanosubstrate (HZnPNS), and we demonstrate its excellent CTC-capture performance along with effective cell-release capability for downstream molecular analysis. This transparent hierarchical architecture prepared by a low-temperature hydrothermal method, enables substantially enhanced capture efficiency and convenient imaging. Biocompatible sodium citrate could rapidly dissolve the architecture at room temperature, allowing that 88 ± 4% of captured cells are gently released with a high viability of 92 ± 1%. Furthermore, antiepithelial cell adhesion molecule antibody functionalized HZnPNS (anti-EpCAM/HZnPNS) was successfully applied to isolate CTCs from whole blood samples of cancer patients, as well as release CTCs for global DNA methylation analysis, indicating it will serve as a simple and reliable alternative platform for CTC detection.
Co-reporter:Heng Xiao, Yuqi Chen, Erfeng Yuan, Wei Li, Zhuoran Jiang, Lai Wei, Haomiao Su, Weiwu Zeng, Yunjiu Gan, Zijing Wang, Bifeng Yuan, Shanshan Qin, Xiaohua Leng, Xin Zhou, Songmei Liu, and Xiang Zhou
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 36) pp:23542
Publication Date(Web):August 23, 2016
DOI:10.1021/acsami.6b07450
Early cancer diagnosis is of great significance to relative cancer prevention and clinical therapy, and it is crucial to efficiently recognize cancerous tumor sites at the molecular level. Herein, we proposed a versatile and efficient strategy based on aptamer recognition and photoactivation imaging for cancer diagnosis. This is the first time that a visible light-controlled photoactivatable aptamer-based platform has been applied for cancer diagnosis. The photoactivatable aptamer-based strategy can accurately detect nucleolin-overexpressed tumor cells and can be used for highly selective cancer cell screening and tissue imaging. This strategy is available for both formalin-fixed paraffin-embedded tissue specimens and frozen sections. Moreover, the photoactivation techniques showed great progress in more accurate and persistent imaging to the use of traditional fluorophores. Significantly, the application of this strategy can produce the same accurate results in tissue specimen analysis as with classical hematoxylin–eosin staining and immunohistochemical technology.Keywords: aptamer; breast cancer; cancer site; fluorescent imaging; nucleolin; photoactivation
Co-reporter:Zhiyong He, Yuqi Chen, Yafen Wang, Jiaqi Wang, Jing Mo, Boshi Fu, Zijing Wang, Yuhao Du and Xiang Zhou
Chemical Communications 2016 vol. 52(Issue 55) pp:8545-8548
Publication Date(Web):10 Jun 2016
DOI:10.1039/C6CC03098J
A new DNA building block (dTetU) bearing a tetrazole and allyloxy group at N-phenyl ring linked through an aminopropynyl linker to the 5-position of 2′-deoxyuridine was synthesized. The modified DNA can be lit up via a photoinduced intramolecular tetrazole–alkene cycloaddition reaction, but quenched when the fully-matched double strand is formed. This conspicuous difference in fluorescence could open a door for DNA single nucleotide polymorphism (SNP) typing.
Co-reporter:Yafen Wang, Chaoxing Liu, Tianlu Wang, Tingting Hong, Haomiao Su, Shuyi Yu, Hongwei Song, Songmei Liu, Xin Zhou, Wuxiang Mao, and Xiang Zhou
Analytical Chemistry 2016 Volume 88(Issue 6) pp:3348
Publication Date(Web):February 9, 2016
DOI:10.1021/acs.analchem.5b04939
DNA methylation is a significant epigenetic modification of the genome that is involved in regulating many cellular processes. An increasing number of human diseases have been discovered to be associated with aberrant DNA methylation, and aberrant DNA methylation has been deemed to be a potential biomarker for diseases such as cancers. A safe, nontoxic, and sensitive method for accurate detection of 5-methylcytosine in genomic DNA is extremely useful for early diagnosis and therapy of cancers. In this paper, we established a novel system to detect 5-methylcytosine, which is based on bisulfite treatment, asymmetric PCR, and specific DNA damaging reagents. Our method could be used for identifying the loci of 5mC in genomic DNA and detecting the DNA methylation levels in tissues as well.
Co-reporter:Shuang Rao, Yuqi Chen, Tingting Hong, Zhiyong He, Shan Guo, Han Lai, Ge Guo, Yuhao Du, and Xiang Zhou
Analytical Chemistry 2016 Volume 88(Issue 21) pp:10547
Publication Date(Web):October 7, 2016
DOI:10.1021/acs.analchem.6b02625
The methylation status of multiplexed methylcytosine sites can be simultaneously monitored by ligation-depended PCR assay. The ability of quantitative detection of multiplexed sites in one PCR reaction makes it a good choice for detecting methylation at both CpG and non-CpG sites for research and diagnosis of disease compared with others. The assay can determine as low as 20 aM methylated DNA and has been successfully applied to the genomic DNA sample derived from cancer cell lines.
Co-reporter:Yingjie Fu, Qishuai Feng, Yifan Chen, Yajing Shen, Qihang Su, Yinglei Zhang, Xiang Zhou, and Yu Cheng
Molecular Pharmaceutics 2016 Volume 13(Issue 9) pp:3308-3317
Publication Date(Web):August 12, 2016
DOI:10.1021/acs.molpharmaceut.6b00619
Drug attachment is important in drug delivery for cancer chemotherapy. The elucidation of the release mechanism and biological behavior of a drug is essential for the design of delivery systems. Here, we used a hydrazone bond or an amide bond to attach an anticancer drug, doxorubicin (Dox), to gold nanoparticles (GNPs) and compared the effects of the chemical bond on the anticancer activities of the resulting Dox-GNPs. The drug release efficiency, cytotoxicity, subcellular distribution, and cell apoptosis of hydrazone-linked HDox-GNPs and amide-linked SDox-GNPs were evaluated in several cancer cells. HDox-GNPs exhibited greater potency for drug delivery via triggered release comediated by acidic pH and glutathione (GSH) than SDox-GNPs triggered by GSH alone. Dox released from HDox-GNPs was released in lysosomes and exerted its drug activity by entering the nuclei. Dox from SDox-GNPs was mainly localized in lysosomes, significantly reducing its efficacy against cancer cells. In addition, in vivo studies in tumor-bearing mice demonstrated that HDox-GNPs and SDox-GNPs both accumulate in tumor tissue. However, only HDox-GNPs enhanced inhibition of subcutaneous tumor growth. This study demonstrates that HDox-GNPs display significant advantages in drug release and antitumor efficacy.Keywords: anticancer activity; doxorubicin; drug delivery; gold nanoparticle;
Co-reporter:Xiaowei Xu, Yuqi Chen, Lai Wei, Wuxiang Mao, Feng Lin and Xiang Zhou
Analytical Methods 2016 vol. 8(Issue 2) pp:245-248
Publication Date(Web):07 Dec 2015
DOI:10.1039/C5AY02267C
We have successfully developed two coumarin-based fluorescent probes to detect F−in vitro. Probe 1 is lipophilic for organic soluted detection. Probe 2 is an amphipathic molecule due to its TBDPS and triphenyl-phosphine groups for both mitochondrial localization and fluoride ion detection. Both of the two probes have good selectivity in F− detection; the detection limit of probe 2 was as low as 670 nM. Probe 2 has good fluorescence enhancement in response to F− in cell imaging. The probes are lowly cytotoxic to cells.
Co-reporter:Tun Tang, Yu-Qi Chen, Bo-Shi Fu, Zhi-Yong He, Heng Xiao, Fan Wu, Jia-Qi Wang, Shao-Ru Wang, Xiang Zhou
Chinese Chemical Letters 2016 Volume 27(Issue 4) pp:540-544
Publication Date(Web):April 2016
DOI:10.1016/j.cclet.2016.01.024
In this study, a resorufin derivative RTP-1, which is a novel fluorescent “turn-on” probe for sensitive detection of hydrazine within 30 min, is designed and synthesized. The selective deprotection of the ester group of the probe by hydrazine led to a prominent enhancement of fluorescent intensity, as well as a remarkable color change from colorless to pink, which could be distinguished by naked eye. The fluorescence enhancement showed decent linear relationship with hydrazine concentration ranging from 0 to 50 μmol/L, with a detection limit of 0.84 μmol/L. The specificity of RTP-1 for hydrazine to a number of metal ions, anions and amines is satisfactory. The sensing mechanism of RTP-1 and hydrazine was evaluated by HPLC, ESI mass spectrometry and density functional theory (DFT). Moreover, we have utilized this fluorescent probe for imaging hydrazine in living cells, and the fluorescence was clearly observed when the cells were incubated with hydrazine (100 μmol/L) for 30 min.A novel resorufin based fluorescent “turn-on” probe could detect hydrazine levels rapidly and applied in living cells.
Co-reporter:Fan Wu, Chaoxing Liu, Yuqi Chen, Shixi Yang, Jiahui Xu, Rong Huang, Xiang Wang, Manjia Li, Wenting Liu, Wuxiang Mao, Xiang Zhou
Sensors and Actuators B: Chemical 2016 Volume 236() pp:268-275
Publication Date(Web):29 November 2016
DOI:10.1016/j.snb.2016.05.162
•We have successfully synthesized a near-infrared fluorescent probe, named PDP-Cy5, realizing visualization of DNA and RNA G-quadruplexes.•PDP-Cy5 had excellent selectivity for G-quadruplexes, eliminating interference of other structures of nucleic acids.•PDP-Cy5 also performed surprising ability to stabilize G-quadruplexes.G-quadruplexes, one of the most significant secondary structure of nucleic acid, are formed by stacking G quartets, which received broad interests due to their involvement in telomere function, gene transcription and recombination. As for ligand, better selectivity for G-quadruplex against other DNA or RNA structures and higher ability to stabilize G-quadruplex are necessary. In addition, developing a new probe to recognize G-quadruplex is desired for utilizing G-quadruplex structure to relevant biological processes. In this study, we report a Cy5 labelled ligand (named PDP-Cy5) developed as a near-infrared fluorescent ligand for G-quadruplexes both in DNA and RNA. The results indicated that PDP-Cy5 selectively induced the formation of intramolecular G-quadruplexes with strong binding affinity. Furthermore, this Cy5 labelled ligand can effectively stabilize G-quadruplexes. Moreover, the direct visualization of G-quadruplexes in gel, even on cell level is realized by using PDP-Cy5.
Co-reporter:Zhenggang Wang;Boshi Fu;Siwei Zou;Bo Duan;Chunyu Chang;Bai Yang
Nano Research 2016 Volume 9( Issue 1) pp:214-223
Publication Date(Web):2016 January
DOI:10.1007/s12274-016-0992-2
To solve the problem of high temperature or long reaction time in hydrothermal synthesis of carbon dots (CDs), a novel method based on the promoting carbonization by hydrochloric acid as catalysis was developed in present work. The acid catalyzed carbon dots (ACDs) were prepared facilely from tryptophan and phenylalanine at 200 °C for 2 h. In our findings, the acids could promote significantly the formation of the ACDs’ carbon core, as a result of the accelerating of the carbonization due to the easy deoxidation. The ACDs showed an average size of 4.8 nm, and consisted of high carbon crystalline core and various surface groups. The ACDs exhibited good optical properties and pH-dependent photoluminescence (PL) intensities. Furthermore, the ACDs were safe and biocompatible. The experimental results demonstrated that such new ACDs were connected with DNA-aptamer by EDC/NHS reaction maintaining both the bright fluorescence and recognizing ability on the cancer cells, which so could be served as an effective PL sensing platform. The resultant DNA-aptamer with ACDs (DNA-ACDs) could stick to human breast cancer cells (MCF-7) specifically, and exhibited high sensitivity and selectivity, indicating the potential applications in the cancer cells targeted imaging fields.
Co-reporter:Shao-Ru Wang;Yuan-Qin Min;Jia-Qi Wang;Chao-Xing Liu;Bo-Shi Fu;Fan Wu;Ling-Yu Wu;Yan-Yan Song;Zhi-Xian Qiao;Guo-Hua Xu;Gai Huang;Zhi-Guo Wu;Nan-Fang Peng;Rong Huang;Wu-Xiang Mao;Shuang Peng;Yu-Qi Chen;Ying Zhu;Tian Tian;Xiao-Lian Zhang
Science Advances 2016 Volume 2(Issue 4) pp:e1501535
Publication Date(Web):01 Apr 2016
DOI:10.1126/sciadv.1501535
A conserved guanine-rich sequence could be a new target for anti–hepatitis C virus drug development.
Co-reporter:Tianlu Wang; Tingting Hong; Yue Huang; Haomiao Su; Fan Wu; Yi Chen; Lai Wei; Wei Huang; Xiaoluan Hua; Yu Xia; Jinglei Xu; Jianhua Gan; Bifeng Yuan; Yuqi Feng; Xiaolian Zhang; Cai-Guang Yang
Journal of the American Chemical Society 2015 Volume 137(Issue 43) pp:13736-13739
Publication Date(Web):October 12, 2015
DOI:10.1021/jacs.5b06690
The FTO protein is unequivocally reported to play a critical role in human obesity and in the regulation of cellular levels of m6A modification, which makes FTO a significant and worthy subject of study. Here, we identified that fluorescein derivatives can selectively inhibit FTO demethylation, and the mechanisms behind these activities were elucidated after we determined the X-ray crystal structures of FTO/fluorescein and FTO/5-aminofluorescein. Furthermore, these inhibitors can also be applied to the direct labeling and enrichment of FTO protein combined with photoaffinity labeling assay.
Co-reporter:Jinjun Wu, Heng Xiao, Tianlu Wang, Tingting Hong, Boshi Fu, Dongsheng Bai, Zhiyong He, Shuang Peng, Xiwen Xing, Jianlin Hu, Pu Guo and Xiang Zhou
Chemical Science 2015 vol. 6(Issue 5) pp:3013-3017
Publication Date(Web):11 Mar 2015
DOI:10.1039/C5SC00484E
N
6-Methyladenosine (m6A) represents a relatively abundant modification in eukaryotic RNA. Because m6A has similar properties to adenosine and a low reactivity, limited research has been focused on this nucleoside. In this study, we revealed an important intermediate in the oxidation of m6A through the bicarbonate-activated peroxide system. Over the course of oxidation, we found a new mechanism in which N6-hydroxymethyladenosine (hm6A), N6-formyladenosine (f6A) and N6-hydroperoxymethyladenosine (oxm6A) were intermediate products, and adenosine was the final product. In this study, oxm6A was isolated using HPLC and characterized by mass spectrometry, NMR and diphenyl-1-pyrenylphosphine (DPPP) fluorescence detection. This study provides a new modified nucleoside and demonstrates oxidative demethylation of m6A by reactive oxygen species at the nucleobase level and in RNA strands.
Co-reporter:Boshi Fu, Jinguo Huang, Dongsheng Bai, Yalun Xie, Yang Wang, Shaoru Wang and Xiang Zhou
Chemical Communications 2015 vol. 51(Issue 95) pp:16960-16963
Publication Date(Web):24 Sep 2015
DOI:10.1039/C5CC04784F
A label-free and biocompatible pH sensor system based on the aggregation-caused quenching (ACQ) probe has been reported herein. The DNA i-motif, a kind of pH-triggered structure, affects the aggregation of PTCDI derivatives by structural switch that would provide significant fluorescence signals responding to the different pH values. Our method not only shows sensitive and reversible response to pH changes, but also could expand the detection range by allosteric control of the DNA i-motif.
Co-reporter:Yuqi Chen, Yanyan Song, Fan Wu, Wenting Liu, Boshi Fu, Bingkun Feng and Xiang Zhou
Chemical Communications 2015 vol. 51(Issue 32) pp:6980-6983
Publication Date(Web):10 Mar 2015
DOI:10.1039/C5CC01389E
A conveniently amplified DNA AND logic gate platform was designed for the highly sensitive detection of low-abundance DNA fragment inputs based on strand displacement reaction and rolling circle amplification strategy. Compared with others, this system can detect miRNAs in biological samples. The success of this strategy demonstrates the potential of DNA logic gates in disease diagnosis.
Co-reporter:Xiwen Xing, Xiaolin Wang, Liang Xu, Yang Tai, Luyang Dai, Xiaolong Zheng, Wuxiang Mao, Xiaowei Xu and Xiang Zhou
Organic & Biomolecular Chemistry 2015 vol. 13(Issue 15) pp:4613-4613
Publication Date(Web):19 Mar 2015
DOI:10.1039/C5OB90054A
Correction for ‘Light-driven conformational regulation of human telomeric G-quadruplex DNA in physiological conditions’ by Xiwen Xing et al., Org. Biomol. Chem., 2011, 9, 6639–6645.
Co-reporter:Tian Tian, Jiaqi Wang and Xiang Zhou
Organic & Biomolecular Chemistry 2015 vol. 13(Issue 8) pp:2226-2238
Publication Date(Web):16 Dec 2014
DOI:10.1039/C4OB02104E
MicroRNA (miRNA) detection is of considerable significance in both disease diagnosis and in the study of miRNA function. The importance of miRNA itself is due to the complicated regulatory functions it plays in various life processes and its close relationship with some diseases. Traditional methods for miRNA detection do not meet the current demands, so various novel methods have been developed with a special focus on sensitivity and specificity. Herein, we summarize and discuss the newly developed miRNA detection methods.
Co-reporter:Jiaqi Wang, Shaoru Wang, Cheng Zhong, Tian Tian and Xiang Zhou
Organic & Biomolecular Chemistry 2015 vol. 13(Issue 34) pp:8996-8999
Publication Date(Web):28 Jul 2015
DOI:10.1039/C5OB01340B
Here, we have provided novel insights into the effects of 8-oxodG substitutions on B–Z transitions of CpG dinucleotide DNAs. A combination of different techniques including a CD study, a PAGE analysis, DFT calculations and molecular modeling has been collectively used.
Co-reporter:Chang-Cheng Wang, Sheng-Yong Yan, Yu-Qi Chen, Yi-Min Zhou, Cheng Zhong, Pu Guo, Rong Huang, Xiao-Cheng Weng, Xiang Zhou
Chinese Chemical Letters 2015 Volume 26(Issue 3) pp:323-328
Publication Date(Web):March 2015
DOI:10.1016/j.cclet.2014.11.029
In this work, triphenylamine pyridine acetonitrile compounds PyA1, PyA2 and PyA3 are designed and synthesized. They show green fluorescence in water and bright emission in solid state. They have large Strokes shift (about 100 nm). The excitation and emission spectra are investigated in ethyl acetate, chloroform, cyclohexane, ethanol, water, acetonitrile, THF, DMF and DMSO. It is interesting to find that these compounds are able to sense increasing pH values ranging from pH 2 to 7 by showing different color and emission intensities: almost no emission at pH 2 and strong green emission at pH 7. The acid–base switched color and fluorescence changes can be observed under UV irradiation, in water solution and 1% agarose gel. These changes can be repeated for several cycles. We are able to employ these compounds for cell pH environment imaging.We have designed three triphenylamine pyridine acetonitrile compounds PyA1, PyA2 and PyA3 as pH sensors, they show green fluorescence at pH 7 while no fluorescence at pH 2, these compounds also can be used for cell pH environment imaging.
Co-reporter:Tun Tang, Yimin Zhou, Yuqi Chen, Mengjun Li, Yan Feng, Changcheng Wang, Shaoru Wang and Xiang Zhou
Analytical Methods 2015 vol. 7(Issue 6) pp:2386-2390
Publication Date(Web):02 Feb 2015
DOI:10.1039/C4AY02922D
Methods based on fluorescent “turn-on” sensors have been developed for methylglyoxal (MGO) detection, but the two-photon one is hardly ever reported. In this study, a naphthalimide derivative PDN-1, which is a novel two-photon fluorescent “turn-on” probe for rapid and sensitive detection of methylglyoxal, is designed and synthesized. Under physiological conditions, the probe showed minimal background emission, whereas, after interacting with MGO, it exhibited significant fluorescence enhancement (33-fold) through the inhibition of the photoinduced electron transfer (PET) effect. The fluorescence enhancement showed a decent linear relationship with the MGO concentration ranging from 0 to 10 μM, with a detection limit of 77 nM. The mechanism of the PDN-1–MGO reaction was evaluated by 1H, 13C NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The specificity of PDN-1 for MGO to other aldehydes, ions, peroxide and nitric oxide is satisfactory. Imaging MGO in living cells by PDN-1 is also accomplished with high sensitivity and low cytotoxicity.
Co-reporter:Fei Ding, Shan Guo, Min Xie, Wei Luo, Chunhui Yuan, Weihua Huang, Yan Zhou, Xiao-Lian Zhang, Xiang Zhou
Talanta 2015 Volume 134() pp:30-36
Publication Date(Web):1 March 2015
DOI:10.1016/j.talanta.2014.09.036
•We select four new aptamers targeting human gastric tumor cells using “Cell-SELEX”.•Aptamers can distinguish human gastric tumor tissues from the normal tissues.•Aptamer-functionalized fluorescent magnetic nanospheres capture 93% cancerous cell.•Aptamer-functionalized fluorescent magnetic nanospheres release 70% cancerous cell.•Aptamer probe can specific detect target gastric tumor cells in vitro and in vivo.Gastric carcinoma is the most malignant tumor. Due to lacking of efficient means to diagnose the cancer at the early stage, it is necessary to develop effective molecular probes for early diagnosis and treatment. We have selected aptamers with high specificity and affinity against SGC7901 cells by cell-SELEX (Systematic Evolution of Ligands by Exponential Enrichment) method, which shown important clinical applications: (1) Specific recognize human gastric tumor tissues compared to the normal tissues. (2)When used to capture cancerous cells, the aptamer-functionalized fluorescent-magnetic nanospheres (FMNS) could specifically capture 93% target cancer cells and about70% target cells can be released. (3) The aptamer probe displayed a quenched fluorescence in the absence of target cancer cells and went through a conformational transformation upon binding to target cancer cells that induced fluorescence. (4) The aptamer probe could target gastric tumors transplanted into mice with obvious fluorescence. The newly generated aptamers hold great potential in early cancer diagnosis.We demonstrated that using cell-SELEX strategy, the selected aptamers could specifically recognize human gastric tumor tissues compared to the normal tissues. When the selected aptamers were conjugated with fluorescent-magnetic nanospheres (FMNS) to capture cancer cells, they showed high captured and release efficiency. The newly designed aptamer probe underwent a conformational change upon binding to the target cancer cell, which resulted in the activation of a fluorescence signal. Flow cytometry assays revealed that the aptamer probe was specifically activated by the target cancer cells and showed high sensitivity for SGC7901 cells. Furthermore, the aptamer probe was able to specifically target the SGC7901 tumor site and exhibited a very bright fluorescence signal within 15 min after injection. The aptamer probe strategy hold a great potential to design molecular probes for in vivo cancer imaging with high sensitivity and specificity.
Co-reporter:Tingting Hong, Tianlu Wang, Zhiyong He, Jingwei Ma, Heng Xiao, Jinguo Huang, Wuxiang Mao and Xiang Zhou
Chemical Communications 2014 vol. 50(Issue 50) pp:6653-6655
Publication Date(Web):02 May 2014
DOI:10.1039/C4CC01933D
The methylation status of each CpG site can be monitored by Fl-dGTP incorporated asymmetric PCR assay. The ability of quantitative detection makes it a good choice for detecting partial methylation at CpG sites compared with others. And the monitoring is not limited to sites within PCR primers or restriction enzyme-recognition sites.
Co-reporter:Shaoru Wang, Boshi Fu, Jiaqi Wang, Yuelin Long, Xiaoe Zhang, Shuang Peng, Pu Guo, Tian Tian, and Xiang Zhou
Analytical Chemistry 2014 Volume 86(Issue 6) pp:2925
Publication Date(Web):February 24, 2014
DOI:10.1021/ac402535a
G-triplex has recently been identified as a new secondary structure in G-rich sequences. However, its functions and biological roles remain largely unknown. This study first developed two kinds of Amplex Red oxidases, which were based on relatively new G-triplex structure and a common G-quadruplex one. A collection of DNA binding assays including circular dichroism (CD) spectroscopy, a CD melting assay, and a UV titration study were used to determine the G-triplex structure of G3 oligomer. The low intrinsic oxidative activity of hemin was significantly enhanced using G-triplex or G-quadruplex. Only one key guanine deletion from the G3 oligomer or G4 one could result in a much decreased Amplex Red oxidation activity. To the best of our knowledge, this is the first case reporting direct use of air as the oxidant for fluorescence generation based on DNAzyme strategies. Further mechanism studies demonstrated an involvement of on-site H2O2 generation from O2 and water and a following oxidation of Amplex Red to resorufin, causing a fluorescence enhancement. Furthermore, the newly developed oxidases have been effectively used in microRNA detection, using only one biotin-labeled probe and one small-molecule substrate. The conjugation of a target DNA to the G-triplex- or G-quadruplex-forming sequence enabled one to produce G-triplex or G-quadruplex by endonuclease in the presence of a slight amount of miRNA and amplify the signal of fluorescence from the oxidation of Amplex Red. Our findings of novel Amplex Red oxidases could potentially be used in a wide range of applications.
Co-reporter:Xi-Wen Xing, Feng Tang, Jun Wu, Jie-Mei Chu, Yu-Qi Feng, Xiang Zhou, and Bi-Feng Yuan
Analytical Chemistry 2014 Volume 86(Issue 22) pp:11269
Publication Date(Web):October 17, 2014
DOI:10.1021/ac502845b
DNA methylation plays vital roles in various biological processes in both prokaryotes and eukaryotes. In bacteria, modification of adenine at N6 can protect bacterial DNA against cleavage by restriction enzymes, and bacterial DNA adenine methyltransferases are essential for bacterial virulence and viability. DNA adenine methyltransferase (DAM) targets the sequence of 5′-GATC-3′ and can convert adenine into N6-methyladenine (m6A). Because mammals do not methylate DNA at adenine, bacterial DAM represents an excellent candidate for antibiotic development. Here, we developed an exonuclease III-aided target recycling strategy to sensitively assay activity of DAM. In this method, a hairpin probe labeled with a donor fluorophore (FAM) at the 5′ end and a quencher (BHQ) close to the 3′ end (FQ probe) was employed as reporter. Another hairpin substrate containing sequence of GATC was used as the methylation substrate of DAM. Once the hairpin substrate was methylated by DAM, it could be recognized and cleaved by Dpn I, which allows the release of a single-stranded oligodeoxynucleotide (ssODN). The ssODN can then hybridize to the 3′ protruding terminus of FQ probe, which subsequently triggers the exonuclease III-mediated target recycling reaction and therefore can significantly improve the detection sensitivity of DAM. The exonuclease-mediated target recycling strategy is extremely sensitive and as low as 0.01 U/mL DAM can be distinctly determined. Using this developed method, we evaluated DAM activity in different growth stages of E. coli cells, and we also demonstrated that the assay has the potential to screen suitable inhibitor drugs for DAM for disease(s) treatment.
Co-reporter:Hai Lai, Yijie Xiao, Shengyong Yan, Fangfang Tian, Cheng Zhong, Yi Liu, Xiaocheng Weng and Xiang Zhou
Analyst 2014 vol. 139(Issue 8) pp:1834-1838
Publication Date(Web):20 Jan 2014
DOI:10.1039/C3AN02269B
In this study, we present a fluorescent switch-on probe based on a cyanovinyl-pyridinium triphenylamine (CPT) derivative that exhibited a 190-fold increase in fluorescence upon binding to G-quadruplex-forming oligonucleotide 22AG. This probe showed specificity and selectivity towards an antiparallel G-quadruplex, indicating its promising potential in G-quadruplex imaging.
Co-reporter:Shuo Feng, Fan Wu, Jiahui Xu, Yuqi Chen and Xiang Zhou
RSC Advances 2014 vol. 4(Issue 98) pp:55367-55370
Publication Date(Web):20 Oct 2014
DOI:10.1039/C4RA09516B
We developed a toehold-mediated DNA strand displacement that is driven only by a G-quadruplex. This strategy is able to be regulated by adjusting the PEG volume fraction, the G-quartet number and the G-quadruplex split mode. This method will provide new possible applications for DNA nanotechnology.
Co-reporter:Fei Ding, Chunhui Yuan, Fan Wu, Shuang Peng, Sufang Tian, Xiao-Lian Zhang and Xiang Zhou
Analytical Methods 2014 vol. 6(Issue 20) pp:8110-8114
Publication Date(Web):03 Jul 2014
DOI:10.1039/C4AY01457J
In this study, we used the “cell-SELEX” strategy to generate four new aptamers with high binding affinity for Huh7.5.1. and HepG2 cells, as indicated by Kd values in the low nanomolar range, as well as high specificity compared to L-02 normal human liver cells. Moreover, the aptamers could distinguish human liver tumour tissues from normal tissues. Incorporation of the aptamer into probes permitted activation by target liver cancer cells to yield enhanced fluorescence and the detection of 103 orders of target liver cancer cells. The newly generated aptamers have great potential in early cancer diagnosis.
Co-reporter:Jianlin Hu, Yuqi Chen, Xiaowei Xu, Fan Wu, Xiwen Xing, Zhenghao Xu, Jiahui Xu, Xiaocheng Weng, Xiang Zhou
Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 11) pp:2589
Publication Date(Web):1 June 2014
DOI:10.1016/j.bmcl.2014.04.027
Co-reporter:Xiaowei Xu, Shengyong Yan, Yimin Zhou, Rong Huang, Yuqi Chen, Jiaqi Wang, Xiaocheng Weng, Xiang Zhou
Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 7) pp:1654-1656
Publication Date(Web):1 April 2014
DOI:10.1016/j.bmcl.2014.02.071
A new kind of aggregation-induced emission compound was synthesized and used as the probe of nucleic acid. The characterization of this compound was studied. Both the RNA and DNA were detected by using this probe. And the detection scope of DNA and RNA was different. We researched the selectivity of our probe in double and single strand DNA sequences. The visualization of gel electrophoresis and the cell nucleus imaging were researched as well. Compared with the traditional nucleus dye Hoechst 33258, our probe also has the potential to be nucleus dye. And the cell toxicity was well performed by MTT assays.
Co-reporter:Jianlin Hu, Yuqi Chen, Xiaowei Xu, Fan Wu, Xiwen Xing, Zhenghao Xu, Jiahui Xu, Xiaocheng Weng, Xiang Zhou
Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 1) pp:294-297
Publication Date(Web):1 January 2014
DOI:10.1016/j.bmcl.2013.11.017
Co-reporter:Jianlin Hu, Fan Wu, Shuo Feng, Jiahui Xu, Zhenghao Xu, Yuqi Chen, Tun Tang, Xiaocheng Weng, Xiang Zhou
Sensors and Actuators B: Chemical 2014 196() pp: 194-202
Publication Date(Web):
DOI:10.1016/j.snb.2014.01.119
Co-reporter:Shuo Feng, Ye Shang, Fan Wu, Fei Ding, Bin Li, Jiahui Xu, Liang Xu, Xiang Zhou
Talanta 2014 Volume 120() pp:141-147
Publication Date(Web):March 2014
DOI:10.1016/j.talanta.2013.11.038
•The amplified MBs(AMBs) were developed based on the structure of kissing-hairpin.•The detections of nucleic acids, proteins and small molecules using AMBs were studied.•AMBs could enhance the detected signals and decrease the sensing limits.•AMBs could distinguish single-base mismatches specifically for nucleic acid detection.•We evaluated the application of AMBs in living cells.Modern biosensors require high sensitivity, great signal enhancement and extensive applicability for detection and diagnostic purposes. Traditional molecular beacons (MBs) do not meet these requirements because of the lack of signal amplification. The current amplification pathways using enzymes, DNAzymes and nanoparticles are usually quite sophisticated and are limited to specific applications. Herein, we developed simple biosensors based on the structure of kissing-hairpin. Through hybridization amplification of these nanomachines, the evolved MBs could greatly enhance the detected signals (approximately 10-fold higher than the signals generated by traditional molecular beacons), reduce the sensing limits for targets and, remarkably, distinguish single-base mismatches specifically for nucleic acid detection. In addition, these new MBs can be directly applied in living cells. By introducing aptamer sequences, these novel sensors can also detect proteins and small molecules. These properties were exemplified by the detection of both the β-actin gene and thrombin. The simplicity, sensitivity and flexibility of these devices make them appropriate for more expansive applications.
Co-reporter:Tianlu Wang ; Tingting Hong ; Tun Tang ; Qianqian Zhai ; Xiwen Xing ; Wuxiang Mao ; Xiaolong Zheng ; Liang Xu ; Jinjun Wu ; Xiaocheng Weng ; Shaoru Wang ; Tian Tian ; Bifeng Yuan ; Bing Huang ; Lin Zhuang
Journal of the American Chemical Society 2013 Volume 135(Issue 4) pp:1240-1243
Publication Date(Web):January 9, 2013
DOI:10.1021/ja311229n
To surmount the challenges of the locus determination and accurate quantification of 5-methyl-2′-deoxycytidine (5MedC) in DNA fragments that contain multiple 5MedC residues, we designed and synthesized two N-halogeno-N-sodiobenzenesulfonamide reagents that provide a new chemical method for probing 5MedC in DNA sequences. When the strategy we provided was combined with β-glucosyltransferase, 5MedC could be distinguished from 5-hydroxymethyl-2′-deoxycytidine (5hmdC) and deoxycytidine (dC) through the introduction of a glucose moiety to the hydroxyl group of 5hmdC.
Co-reporter:Shaoru Wang ; Yuelin Long ; Jiaqi Wang ; Yushu Ge ; Pu Guo ; Yi Liu ; Tian Tian
Journal of the American Chemical Society 2013 Volume 136(Issue 1) pp:56-59
Publication Date(Web):December 23, 2013
DOI:10.1021/ja4107012
We have first demonstrated the distinctive effects of three newly reported epigenetic modifications, including 5hmC, 5fC, and 5caC, on B-Z transition of CpG dinucleotide DNAs. We have performed detailed assays and compared their effects. We further studied the regulation of B-Z transition of CpG dinucleotide dodecamers by alternating oxidation and alternating reduction.
Co-reporter:Shaoru Wang, Boshi Fu, Shuang Peng, Xiaoe Zhang, Tian Tian and Xiang Zhou
Chemical Communications 2013 vol. 49(Issue 72) pp:7920-7922
Publication Date(Web):26 Jun 2013
DOI:10.1039/C3CC44075C
This study is the first to investigate the interactions of hemin with a G-triplex DNA of T1 using different DNA binding assays. The low intrinsic peroxidatic activity of hemin could be significantly enhanced using T1. Furthermore, much decreased oxidation enhancement by T2 or T3 with one key guanine mutation was observed, and the observed peroxidatic activity of T1 should be directly due to the G-triplex complexed with hemin.
Co-reporter:Tian Tian, Xiaoe Zhang, Boshi Fu, Yuelin Long, Shuang Peng, Shaoru Wang, Xiang Zhou and Xin Zhou
Chemical Communications 2013 vol. 49(Issue 85) pp:9968-9970
Publication Date(Web):20 Aug 2013
DOI:10.1039/C3CC45423A
We have conducted the first systematic investigation of DNAs with modified cytosines, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), under hot alkali treatment.
Co-reporter:Tian Tian, Shuang Peng, Heng Xiao, Yuelin Long, Boshi Fu, Xiaoe Zhang, Shan Guo, Shaoru Wang, Xiang Zhou, Songmei Liu and Xin Zhou
Chemical Communications 2013 vol. 49(Issue 86) pp:10085-10087
Publication Date(Web):05 Sep 2013
DOI:10.1039/C3CC44017F
Here, we first demonstrated that 5-MedCTP could be incorporated into the synthetic DNA template by the exonuclease deficient Klenow fragment with a much higher efficiency than dCTP and 5-hydroxymethyl-dCTP. Further, we first conducted a comparable study of primer extension reaction using templates containing deoxycytidine (dC) or 5-methyldeoxycytidine (5-mdC) for incorporating different triphosphates. Based on our findings, 5-methyldeoxycytidine could enhance the substrate activity of the Klenow fragment (exo-) and this feature could potentially be used in DNA methylation analysis.
Co-reporter:Tian Tian, Shuang Peng, Heng Xiao, Xiaoe Zhang, Shan Guo, Shaoru Wang, Xiang Zhou, Songmei Liu and Xin Zhou
Chemical Communications 2013 vol. 49(Issue 26) pp:2652-2654
Publication Date(Web):11 Feb 2013
DOI:10.1039/C3CC38818B
The present study demonstrated a highly sensitive strategy for measuring telomerase activity in cell extracts. Furthermore, we applied the new strategy for in situ detection of telomerase at the cellular level in cancer cells, together with a normal cell as the negative control.
Co-reporter:Tian Tian, Heng Xiao, Xiaolian Zhang, Shuang Peng, Xiaoe Zhang, Shan Guo, Shaoru Wang, Songmei Liu, Xin Zhou, Craig Meyers and Xiang Zhou
Chemical Communications 2013 vol. 49(Issue 1) pp:75-77
Publication Date(Web):05 Nov 2012
DOI:10.1039/C2CC36728A
We reported an efficient strategy based on a strand displacement amplification for serum miRNA detection. In such a system, a multiplexed, sensitive and quick detection of miRNAs could be achieved through a combination of fluorescence labeled probes, a common primer and a polymerase. This could be potentially used in the clinical field to achieve early disease diagnosis and prognosis.
Co-reporter:Pu Guo, Shengyong Yan, Jianlin Hu, Xiwen Xing, Changcheng Wang, Xiaowei Xu, Xiaoyu Qiu, Wen Ma, Chunjiang Lu, Xiaocheng Weng, and Xiang Zhou
Organic Letters 2013 Volume 15(Issue 13) pp:3266-3269
Publication Date(Web):June 14, 2013
DOI:10.1021/ol401290d
Fluorogenic hydroxylamine reagents were used for detecting 5-fC through a labeling pathway. Chemical synthesis, HPLC, denaturing PAGE, and DNA MS were applied to testify that the probe reacted with 5-fC with oligodeoxynucleotide selectivity to achieve 5-fC detection conveniently and quantificationally with the method of fluorescence. The feasibility of fluorescently detecting 5-fC in a genome was also investigated.
Co-reporter:Tingting Hong, Tianlu Wang, Pu Guo, Xiwen Xing, Fei Ding, Yuqi Chen, Jinjun Wu, Jingwei Ma, Fan Wu, and Xiang Zhou
Analytical Chemistry 2013 Volume 85(Issue 22) pp:10797
Publication Date(Web):September 2, 2013
DOI:10.1021/ac4020676
DNA methylation is dynamically reprogrammed during early embryonic development in mammals. It can be explained partially by the discovery of 5-(hydroxymethyl)cytosine (5-hmC), 5-formylcytosine (5-fC), and 5-carboxylcytosine (5-caC), which are identified as key players involved in both active and passive demethylation pathways. As one of the ten–eleven translocation oxidation products, 5-hmC was found relatively abundant in neuron cells and embryonic stem cells. Herein we report a new method for 5-hmC quantification in genomic DNA based on CCP-FRET (cationic conjugated polymers act as the energy donor and induce fluorescence resonance energy transfer) assay combined with KRuO4 oxidation. 5-hmC in genomic DNA can be selectively transformed into 5-fC by the oxidation of KRuO4 and then labeled with hydroxylamine-BODIPY (BODIPY = 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophore through the reaction between 5-fC and hydroxylamine-BODIPY. After the fluorescently labeled DNA was captured by CCP through electrostatic interactions, a significant FRET between CCP and hydroxylamine-BODIPY fluorophore was observed. This CCP-FRET-based assay benefits from light-harvesting, large Stokes shift, and optical signal amplification properties of the CCP. Furthermore, this CCP-FRET-based assay was quite successfully demonstrated for the 5-hmC quantification in three types of cells (mESc, HeLa, HEK 293T), providing a much more convenient choice for 5-hmC quantification in genomic DNA.
Co-reporter:Changcheng Wang, Shengyong Yan, Rong Huang, Shuo Feng, Boshi Fu, Xiaocheng Weng and Xiang Zhou
Analyst 2013 vol. 138(Issue 10) pp:2825-2828
Publication Date(Web):21 Mar 2013
DOI:10.1039/C3AN00272A
We have presented a fluorescent probe that exhibits a fluorescence turn-on signal upon reaction with tyrosinase, and we show that it can be readily employed for the assessment of tyrosinase activity and tyrosinase inhibitor activities in buffered aqueous solution.
Co-reporter:Pu Guo, Shengyong Yan, Yimin Zhou, Changcheng Wang, Xiaowei Xu, Xiaocheng Weng and Xiang Zhou
Analyst 2013 vol. 138(Issue 12) pp:3365-3367
Publication Date(Web):25 Mar 2013
DOI:10.1039/C3AN00375B
Acid phosphatase (ACP) can be sensitively, conveniently and efficiently detected via a new fluorescent “Turn-Off/Turn-On” system. Inexpensive (NaPO3)6 is carefully introduced into this system as a quencher of the aggregation-caused quenching (ACQ) probe. In our method, the limit of detection (LOD) is quite low for detecting ACP, which is an important biomarker and indication of several diseases.
Co-reporter:Jun Wu, Rong Huang, Changcheng Wang, Wenting Liu, Jiaqi Wang, Xiaocheng Weng, Tian Tian and Xiang Zhou
Organic & Biomolecular Chemistry 2013 vol. 11(Issue 4) pp:580-585
Publication Date(Web):02 Nov 2012
DOI:10.1039/C2OB26680F
A new bifunctional compound NCC, which undergoes thiol-mediated disulfide cleavage after cell entry, produces a red-shifted fluorescent emission in the cytosol and releases free active DNA alkylating agent CLB into the nucleus, and finally leads to DNA damage and cell death.
Co-reporter:Pu Guo, Xiaowei Xu, Xiaoyu Qiu, Yimin Zhou, Shengyong Yan, Changcheng Wang, Chunjiang Lu, Wen Ma, Xiaocheng Weng, Xianzheng Zhang and Xiang Zhou
Organic & Biomolecular Chemistry 2013 vol. 11(Issue 10) pp:1610-1613
Publication Date(Web):22 Jan 2013
DOI:10.1039/C3OB27519A
Fluorescent nucleosides (dUbmz) with desirable fluorescence quantum yield (Φ) are synthesized from almost non-fluorescent 5-fdU and o-phenylenediamine derivatives. The fluorescence of these nucleosides is quite sensitive to pH and organic solvents. 4-Methoxybenzene-1,2-diamine was used for the detection of 5-fdU among natural nucleosides.
Co-reporter:Jun Wu, Rong Huang, Tianlu Wang, Xi Zhao, Wanyi Zhang, Xiaocheng Weng, Tian Tian and Xiang Zhou
Organic & Biomolecular Chemistry 2013 vol. 11(Issue 14) pp:2365-2369
Publication Date(Web):04 Jan 2013
DOI:10.1039/C2OB27324A
Two new small compounds, which undergo fluoride-mediated self rearrangement, produce active DNA alkylating agent nitrogen mustard leading to DNA damage and finally cell death, providing potential antitumor prodrugs.
Co-reporter:Wuxiang Mao, Jianlin Hu, Tingting Hong, Xiwen Xing, Sen Wang, Xi Chen and Xiang Zhou
Organic & Biomolecular Chemistry 2013 vol. 11(Issue 21) pp:3568-3572
Publication Date(Web):27 Mar 2013
DOI:10.1039/C3OB40447A
Treatment of DNA containing 5-formylcytosine with hot piperidine produced a cleaved band at the position of 5-formylcytosine in DNA sequences. After oxidation with KRuO4, 5-hydroxymethylcytosine could also be detected using the same method. Using our strategy, we could detect 5-hydroxymethylcytosine and 5-formylcytosine respectively.
Co-reporter:Shengyong Yan, Xiaowei Xu, Pu Guo, Jianlin Hu, Changcheng Wang, Rong Huang, Xiaocheng Weng, Yuhao Du and Xiang Zhou
RSC Advances 2013 vol. 3(Issue 30) pp:12066-12068
Publication Date(Web):04 Jun 2013
DOI:10.1039/C3RA41669K
A new type of 1,3-O,N-heterocycle, including two fluorescent derivatives, has been synthesised by the reaction of the hydroxyl and amine groups of 5-hydroxymethyl-2′-deoxycytidine (hmC). This reactivity is shown to enable the selective recognition of hmC over other natural nucleotides in aqueous buffer.
Co-reporter:Yanli Ge, Xiaocheng Weng, Tian Tian, Fei Ding, Rong Huang, Libo Yuan, Jun Wu, Tianlu Wang, Pu Guo and Xiang Zhou
RSC Advances 2013 vol. 3(Issue 31) pp:12839-12846
Publication Date(Web):10 May 2013
DOI:10.1039/C3RA41647J
A water-soluble zinc(II) phthalocyanine (ZnPc1) substituted with 1-(3-methyl) imidazoliumylethyloxy on the periphery was synthesized, and its subcellular localization and photodynamic activities were studied. ZnPc1 exhibited an almost exclusive mitochondrial-localizing property in human cervical carcinoma (HeLa) cells. Remarkable photocytotoxicity but low dark cytotoxic properties were observed for ZnPc1 in four different cancer cell lines. Photodynamic treatment (PDT) with ZnPc1 resulted in the generation of reactive oxygen species, a collapse of the mitochondrial membrane potential and chromatin condensation, all important hallmarks of apoptosis. The results are consistent with its mitochondrial localization property and qualify ZnPc1 as a promising PDT agent.
Co-reporter:Wenting Liu, Lingyu Wu, Shengyong Yan, Rong Huang, Xiaocheng Weng and Xiang Zhou
Analytical Methods 2013 vol. 5(Issue 15) pp:3631-3634
Publication Date(Web):13 Jun 2013
DOI:10.1039/C3AY40581H
Based on graphene oxide and Hoechst 33258, bioassays towards target DNA and several enzymes including Exo III and Dam MTase were established. This strategy eliminates the need for modification of oligonucleotides, and can give similarly satisfactory results compared to traditional methods using labelled DNA. Moreover, “AND” and “INHIBIT” dual-output DNA logic gates were developed.
Co-reporter:Lin Liu, Qianqian Zhai, Tingting Hong, Yushu Ge, Peng Hu, Xiaocheng Weng, Yi Liu, Xiang Zhou
Inorganica Chimica Acta 2013 Volume 394() pp:385-390
Publication Date(Web):1 January 2013
DOI:10.1016/j.ica.2012.08.021
Ruthenium complexes are well known for their high affinity and reactivity with DNA. There are so many reports about the interactions of ruthenium complexes and duplex DNA. However, their effects on other DNA structures are poorly studied. In this paper, the photo-activated DNA cleavage by two ruthenium(II) complexes was researched. It was found that these complexes can selectively act on the guanosine bases located in DNA non-duplex portions which were contained in the well matched duplex structures. The mechanism was also studied and considered to be a singlet oxygen oxidation. Through the molecular modeling experiment, we proposed that the strong interaction of complexes with non-duplex DNA structure cause the structural selectivity of DNA cleavage. The research show great future prospects of these ruthenium complexes to be used in anticancer drug development and nucleic acid structure research.Graphical abstractThe ruthenium(II) complexes could selectively cleave the guanosine bases in loop and bulge but have no cleavage reaction in the duplex portion.Highlights► The photo-activated DNA cleavage by two ruthenium(II) complexes was researched. ► The complexes can selectively cleave the G-base which located in the non-duplex region. ► The interaction of complexes with DNA was simulated by the molecular modeling experiments. ► The strong interaction of complexes with non-duplex DNA structure leads the selectivity.
Co-reporter:Dr. Tian Tian;Heng Xiao;Zhengan Zhang;Yuelin Long;Shuang Peng;Dr. Shaoru Wang;Dr. Xiang Zhou;Dr. Songmei Liu; Xin Zhou
Chemistry - A European Journal 2013 Volume 19( Issue 1) pp:92-95
Publication Date(Web):
DOI:10.1002/chem.201203344
Co-reporter:Xiaowei Xu, Shengyong Yan, Jianlin Hu, Pu Guo, Lai Wei, Xiaocheng Weng, Xiang Zhou
Tetrahedron 2013 69(46) pp: 9870-9874
Publication Date(Web):
DOI:10.1016/j.tet.2013.08.069
Co-reporter:Jianlin Hu;Xiwen Xing;Xiaowei Xu;Fan Wu;Pu Guo;Shengyong Yan;Zhenghao Xu;Jiahui Xu;Dr. Xiaocheng Weng ; Xiang Zhou
Chemistry - A European Journal 2013 Volume 19( Issue 19) pp:5836-5840
Publication Date(Web):
DOI:10.1002/chem.201300082
Co-reporter:Rong Huang, Jiaqi Wang, Wuxiang Mao, Boshi Fu, Xiwen Xing, Ge Guo, Xiang Zhou
Talanta 2013 Volume 117() pp:445-448
Publication Date(Web):15 December 2013
DOI:10.1016/j.talanta.2013.09.026
•The combined bisulfite UDG assay can be used to detect effectively and specifically the amount and location of 5-methylcytosine residues regardless of sequence context.•This approach provides linearly quantitative assessments of DNA methylation across a wide range of methylation levels.•This assay has the potential to enable profiling of methylation levels in genomic DNA, which will be pursued in future work.DNA modification, a significant epigenetic event, largely affects genes' binding with the transcription factors and some other DNA binding proteins. Among DNA modifications, methylation, especially cytosine methylation is of great importance and attracts extensive studies as it leads to the silence of tumor-suppressor gene expression. In this work, a novel combined bisulfite Uracil-DNA glycosylase (UDG) assay has been developed on the basis of bisulfite modification to generate uracil from cytosine, subsequent UDG-mediated uracil elimination and ultimate DNA cleavage in alkaline condition. This strategy can be used to selectively detect exact number and loci of 5-methylcytosine residues regardless of sequence context. Moreover, it provides linear quantitative results of DNA methylation level across a wide range.
Co-reporter:Tian Tian, Heng Xiao, Yuelin Long, Xiaoe Zhang, Shaoru Wang, Xiang Zhou, Songmei Liu and Xin Zhou
Chemical Communications 2012 vol. 48(Issue 80) pp:10031-10033
Publication Date(Web):23 Aug 2012
DOI:10.1039/C2CC35648A
The analysis of DNA methylation and MTase (methyltransferase) activity is important in epigenetic study. We have developed a novel strategy for sensitive analysis of MTase activity based on a hairpin shaped DNAzyme; 8–17 DNAzyme amplicon has been adopted and found to be very effective in such analysis.
Co-reporter:Rong Huang, Shengyong Yan, Xiaolong Zheng, Fengling Luo, Minggang Deng, Boshi Fu, Yijie Xiao, Xi Zhao and Xiang Zhou
Analyst 2012 vol. 137(Issue 19) pp:4418-4420
Publication Date(Web):24 Jul 2012
DOI:10.1039/C2AN35671F
Novel pH-activatable fluorescent probes with various pKa values have been developed utilizing 4-nitro-benzo[1,2,5]oxadiazole derivatives (NBD) as fluorophores and piperazine moieties as proton receptors. Under acidic conditions, probe FoPz displayed significant fluorescent enhancement of about 30 fold with a pKa value of 5.70 and it responds rapidly and sensitively to intracellular pH distributions and cellular pH fluctuations.
Co-reporter:Liang Xu, Weixin Wu, Jie Ding, Shuo Feng, Xiwen Xing, Minggang Deng and Xiang Zhou
RSC Advances 2012 vol. 2(Issue 3) pp:894-899
Publication Date(Web):30 Nov 2011
DOI:10.1039/C1RA00851J
G-Quadruplexes formed by G-rich DNA are of broad interest due to their involvement in telomere function, gene transcription and recombination. Small ligands that interact strongly with G-quadruplexes have been considered to further influence telomeric function and gene transcription. Because most G-rich sequences are trapped in duplex structures in gene promoters, ligands that can stabilize G-quadruplexes in the presence of their complimentary strands would likely have strong effects on gene transcription. Here, we report a novel simple small molecule (pyridyl carboxamide), consisting of three pyridine rings and four amide bonds. Comparing with some reported G-quadruplex ligands, this molecule not only selectively stabilizes G-quadruplexes rather than duplexes, but also maintains a G-quadruplex structure even if the G-rich region was trapped in long double-stranded DNA (dsDNA). It is widely believed that the dissociation of duplexes is involved in gene transcription and that the formation of the G-quadruplex influences some oncogene expression. Py-Am exhibited strong G-quadruplex-forming ability within a long dsDNA sequence, suggesting it would have potent effects on the G-quadruplex-forming sequences involved in gene transcription.
Co-reporter:Changcheng Wang;Xiaolong Zheng;Rong Huang;Shengyong Yan;Xia Xie;Tian Tian;Shiwen Huang;Xiaocheng Weng
Asian Journal of Organic Chemistry 2012 Volume 1( Issue 3) pp:259-263
Publication Date(Web):
DOI:10.1002/ajoc.201200061
Abstract
Palladium is a member of the platinum group of metals and can be used in the electronics industry for applications such as preparing precision resistors. It is also utilized for catalysis in organic chemistry to achieve faster reaction speeds and lower costs of production in industry. Overexposure to Pd is harmful to the environment and to human health because it can be conveyed quickly to the liver, kidney, spleen, adrenal glands, lungs, and bones. Herein, a fluorescent probe that contains an alkynyl group for specific reaction with PdII ions, and a naphthalimide group as a fluorophore was designed. This probe has high specificity and selectivity for PdII ions relative to many other metal ions. HPLC analysis was carried out to verify the mechanism of the detection. There is a distinct color change during the detection process. The influence of pH values shows that the probe is suitable to detect PdII ions in the range pH 6–9.
Co-reporter:Fei Ding;Jun You;Xiaocheng Weng;Jinping Zhou;Xiaolian Zhang;Lina Zhang
Chinese Journal of Chemistry 2012 Volume 30( Issue 9) pp:2212-2218
Publication Date(Web):
DOI:10.1002/cjoc.201200659
Abstract
Cationic polysaccharides have been receiving more attentions and used as nonviral gene delivery vectors. In this paper, quaternized hydroxyethylcellulose (QHEC) derivatives were studied as gene carriers for their efficient DNA binding abilities. All QHECs could form stable QHEC/DNA complexes and resist the degradation of DNase I. And the dynamic light scatter (DLS) results showed that all QHEC/DNA complexes could form compact particles. These QHEC/DNA complexes exhibited effective transfection abilities in comparison to the naked DNA. The cytotoxicities of QHEC and QHEC/DNA complexes were also evaluated in four cell lines which were relatively low compared with 25 kDa bPEI. All results indicated that these quaternized hydroxyethylcelluloses could be used as potential gene delivery vectors.
Co-reporter:Lin Liu, Wenting Liu, Tingting Hong, Xiaocheng Weng, Qianqian Zhai and Xiang Zhou
Analytical Methods 2012 vol. 4(Issue 7) pp:1935-1939
Publication Date(Web):09 May 2012
DOI:10.1039/C2AY25362C
Sensitive and selective techniques for both Ag+ and Cys detection have been designed based on graphene oxide (GO) and G-quadruplex DNA. The G-quadruplex structure can capture the fluorescent molecule acridine orange (AO) from the surface of graphene oxide (GO), which will recover the fluorescence of AO that was initially quenched by GO. Then the addition of Ag+ will release AO back to GO, because Ag+ can destroy the G-quadruplex structure, giving a fluorescence quenching process again. Based on this “turn off” principle, a highly sensitive and selective Ag+ detection method was developed. In addition, cysteine (Cys) can capture Ag+ from the guanine base of DNA which will result in the regeneration of the G-quadruplex DNA structure and thus the regeneration of the fluorescence signal. This “turn on” principle can be used for the development of a highly selective and sensitive detection method for Cys.
Co-reporter:Liang Xu, Zhouxin Xu, Ye Shang, Shuo Feng, Xiang Zhou
Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 8) pp:2988-2992
Publication Date(Web):15 April 2012
DOI:10.1016/j.bmcl.2012.02.030
In this work, we described a kinetically slow (hour-scale) but thermodynamically favored G-quadruplex conversion induced by a pyridyl carboxamide molecule. This slow transition was observed through CD spectra and gels, and its final stable parallel conformation was identified by 2-aminopurine experiments. Kinetic experiments indicated that this slow process was a first-order reaction, implying it was a unimolecular conversion. Quite distinctly from other reported ligand-driven G-quadruplex conformation alteration, this slow conversion reveals a novel insight into G-quadruplex polymorphism, in accordance with the behavior of human telomere G-quadruplex in a molecular crowding environment in K+ solution, further enriching the known structural polymorphism of human telomere DNA and providing new consideration for drug design based on G-quadruplexes.
Co-reporter:Qianqian Zhai, Minggang Deng, Liang Xu, Xiaolian Zhang, Xiang Zhou
Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 2) pp:1142-1145
Publication Date(Web):15 January 2012
DOI:10.1016/j.bmcl.2011.11.099
In the study, we demonstrated that freezing was able to facilitate the short DNA strand T4G4 to self-assemble into a tetramolecular G-quadruplex with a low DNA concentration in the absence of any ligand, providing a fast approach to configure intermolecular G-quadruplexes. The fast formation of intermolecular G-quadruplexes may offer a convenient tool.Freezing was able to facilitate the short DNA strand T4G4 to self-assemble into tetramolecular G-quadruplexes with a low DNA concentration.
Co-reporter:Ming Zhang;Haiqun Li;Minggang Deng;Xiaocheng Weng;Heng Ma;Shuo Feng;Yangyang Zhou
Chemistry & Biodiversity 2012 Volume 9( Issue 1) pp:170-180
Publication Date(Web):
DOI:10.1002/cbdv.201100040
Abstract
In the presence of hemin and under appropriate conditions, some modalities of G-quadruplexes can form a peroxidase-like DNAzyme that has been widely used in biology. Structurefunction studies on the DNAzyme revealed that its catalytic ability may be dependent on the unimolecular parallel G-quadruplex. In this report, we present the preliminary investigation on the relationship between the structure and function of DNAzymes through a terminal oligo modification in G-quadruplex sequences by adding different lengths of oligo-dT to the 3′- or 5′-end of the aptamers. The results suggested that adding dTn to the 5′-end of the DNA sequence of the enzyme improved the ability of hemin to bind with DNA, but the addition of dTn to the 3′-end decreased the binding ability of hemin for DNA. The increased stability of the assembled DNAzyme would lead to more favorable binding between the enzyme and substrate (H2O2), facilitating higher peroxidase activity; on the contrary, with lower stability of the DNAzyme complex, we observed reduced peroxidase activity.
Co-reporter:Shengyong Yan;Rong Huang;Changcheng Wang;Yimin Zhou;Jiaqi Wang;Boshi Fu;Xiaocheng Weng;Dr. Xiang Zhou
Chemistry – An Asian Journal 2012 Volume 7( Issue 12) pp:2782-2785
Publication Date(Web):
DOI:10.1002/asia.201200762
Co-reporter:Rong Huang;Xiaolong Zheng;Changcheng Wang;Renyi Wu;Shengyong Yan;Jiaqi Yuan; Xiaocheng Weng;Dr. Xiang Zhou
Chemistry – An Asian Journal 2012 Volume 7( Issue 5) pp:915-918
Publication Date(Web):
DOI:10.1002/asia.201101028
Co-reporter:Liang Xu, Shuo Feng and Xiang Zhou
Chemical Communications 2011 vol. 47(Issue 12) pp:3517-3519
Publication Date(Web):10 Feb 2011
DOI:10.1039/C0CC05242F
We provide a novel insight into dynamic conversion of the human telomeric G-quadruplexes and particularly a step-to-step transformation pathway of the long sequence containing two quadruplex units in K+ solution in a molecular crowding environment, implying a possible behavior of the human telomeric DNA under physiological conditions.
Co-reporter:Shengyong Yan, Rong Huang, Yangyang Zhou, Ming Zhang, Minggang Deng, Xiaolin Wang, Xiaocheng Weng and Xiang Zhou
Chemical Communications 2011 vol. 47(Issue 4) pp:1273-1275
Publication Date(Web):22 Nov 2010
DOI:10.1039/C0CC02792H
In this thrombin detection system, the bright fluorescence of TASPI is almost eliminated by the DNA aptamer TBA (turn-off); however, in the presence of thrombin, it specifically binds to TBA by folding unrestricted TBA into an anti-parallel G-quadruplex structure and then releasing TASPI molecules, resulting in vivid and facile fluorescence recovery (turn-on).
Co-reporter:Yangyang Zhou, Minggang Deng, Yuanyuan Du, Shengyong Yan, Rong Huang, Xiaocheng Weng, Chuluo Yang, Xiaolian Zhang and Xiang Zhou
Analyst 2011 vol. 136(Issue 5) pp:955-961
Publication Date(Web):15 Dec 2010
DOI:10.1039/C0AN00927J
In the present work, a novel water-soluble cationic triazatetrabenzcorrole compound was synthesised. Its aggregation and fluorescence quenching properties are demonstrated by serval methods, such as UV-vis and fluorescence spectroscopic studies and naked-eye visualization. Unlike the traditional Hg2+ sensor based on thymine–Hg2+–thymine, we use a novel approach, exploiting the high affinity of Hg2+ for sulfur in phosphorothioate DNA. Based on the S–Hg2+–S pairs, we designed the phosphorothioate DNA T4G4-S3 as an Hg2+ sensor, which can detect Hg2+ sensitively and selectively in aqueous solution. And this sensing system is fairly fast and convenient.
Co-reporter:Xiwen Xing, Xiaoling Wang, Liang Xu, Yang Tai, Luyang Dai, Xiaolong Zheng, Wuxiang Mao, Xiaowei Xu and Xiang Zhou
Organic & Biomolecular Chemistry 2011 vol. 9(Issue 19) pp:6639-6645
Publication Date(Web):27 Jun 2011
DOI:10.1039/C1OB05939D
Human telomeric G-quadruplexes have raised broad interest not just due to their involvement in the regulation of gene expressions and telomerase activities but also because of their application in nanoarchitectures. Herein, three azobenzene derivatives 1–3 were synthesized with different substituent groups and their photo-isomerization properties were investigated by UV/Vis spectroscopy. Then circular dichroism spectroscopy (CD), fluorescence experiments and native-gel electrophoresis were performed to evaluate their capabilities of conformational photo-regulation both in the absence and presence of metal ions. The results suggested that the compounds synthesized can successfully regulate the conformation of human telomeric G-quadruplex DNA in K+ conditions to some extent. This work will initiate the possibility for the design and intriguing application of light-induced switching to photoregulate the conformation of G-quadruplex DNA under physiological conditions, providing a possible pathway to control G-quadruplex conformation in biological applications and also expanding the potential use of G-quadruplexes in nanomachines.
Co-reporter:Zhiguo Wu;Dr. Tian Tian;Dr. Junping Yu; Xiaocheng Weng; Yi Liu; Xiang Zhou
Angewandte Chemie International Edition 2011 Volume 50( Issue 50) pp:11962-11967
Publication Date(Web):
DOI:10.1002/anie.201104422
Co-reporter:Qianqian Zhai;Liang Xu;Yushu Ge;Dr. Tian Tian;Wendi Wu;Shengyong Yan;Yangyang Zhou;Dr. Minggang Deng; Yi Liu
Chemistry - A European Journal 2011 Volume 17( Issue 32) pp:8890-8895
Publication Date(Web):
DOI:10.1002/chem.201101128
Abstract
DNA damage plays an important role in cellular processes. Besides natural protein nucleases, different types of efficient agents for DNA damage have been developed over recent decades in the search for new anticancer and antiviral drugs. In addition to the double-stranded configuration, DNA structures also include some non-duplex regions, which are considered to be from spontaneous errors in DNA replication, thus playing an important role for cells. Herein, we focused on these non-duplex regions of DNA and generated manganese(III) corroles, which exhibit a highly selective cleavage ability for guanosine units located at non-duplex portions, such as loops and bulges. The cleavage mechanism was demonstrated to be a manganese-induced oxidation process. The results given herein show a molecular approach that could specifically probe the guanosine units in DNA non-duplex structures, thus representing a promising step in the construction of tools to target non-duplex structures in chromosomes.
Co-reporter:Zhiguo Wu, Mingliang Tang, Tian Tian, Jianguo Wu, Yuanlin Deng, Xiaohu Dong, Zheng Tan, Xiaocheng Weng, Zhihong Liu, Chunjiang Wang, Xiang Zhou
Talanta 2011 Volume 87() pp:216-221
Publication Date(Web):15 December 2011
DOI:10.1016/j.talanta.2011.09.065
Lysosomes are vital organelles in physiological processes, as they receive and degrade macromolecules from the secretory and endocytic procedures. Evidences have shown that lysosomes were related to oncogenic activation and cancer progression, so lysosomes targeting and imaging probes make them convenient to be observed. In this study, a lysosome specific probe W-7 was designed and synthesized via convenient one-pot reaction and Heck reaction. This probe was derived from Tröger's base with a dimethylaminomethyl end group. The optical properties of this compound were measured. W-7 also showed two-photon absorption (TPA) effect by using laser excitation at the wavelength of infrared light. In vivo experiment, W-7 showed high specificity and selectivity for lysosomes in living cells (HeLa cells, MRC-5 cells and NRK cells), compared with LT Red, GT Red and MT Red (R = 0.96). Two-photon fluorescence images of HeLa cells stained by W-7 were obtained. And high resolution 3D reconstruction of lysosomes in one HeLa cell was provided by using two-photon confocal microscopy. The anantioseparation of racemic W-7 was carried out by chiral-HPLC, and the two enantiomers showed no significant difference in lysosomes imaging.Highlights► In this manuscript, we reported that a lysosomal probe derived from Tröger's base for two-photon fluorescence imaging was designed and synthesized. ► This probe showed high specificity and selectivity for lysosomes, and the Pearson's correlation coefficient is 0.96. ► It also provided high resolution 3D reconstruction of lysosomes in one HeLa cell by using two-photon confocal microscopy.
Co-reporter:Tian Tian;ShaoRu Wang;JianGuo Wu
Science China Chemistry 2011 Volume 54( Issue 8) pp:
Publication Date(Web):2011 August
DOI:10.1007/s11426-011-4318-7
DNA methylation is one of the most signaficant epigenetic events which greatly influence gene activation, gene imprinting, chromatin stability, and so on. The level of methylation in genome and certain regions should be in a normal range, because any variation would cause physiological dysfunction. In account of essential roles of DNA methylation in the living system, the detection of methylation in both overall genome and specific positions has drawn great interest. So far many biological and chemical methods have been developed to detect DNA methylation. Herein, we summerize some novel methods mainly based on chemical modification and analytic methods in DNA detection.
Co-reporter:Zhiguo Wu;Dr. Tian Tian;Dr. Junping Yu; Xiaocheng Weng; Yi Liu; Xiang Zhou
Angewandte Chemie 2011 Volume 123( Issue 50) pp:12168-12173
Publication Date(Web):
DOI:10.1002/ange.201104422
Co-reporter:Minghui Bai, Jing Huang, Xiaolong Zheng, Zhibin Song, Miru Tang, Wuxiang Mao, Libo Yuan, Jun Wu, Xiaocheng Weng, and Xiang Zhou
Journal of the American Chemical Society 2010 Volume 132(Issue 43) pp:15321-15327
Publication Date(Web):October 12, 2010
DOI:10.1021/ja106637e
A series of bis(catechol) quaternary ammonium derivatives were designed and synthesized. We investigated their ability to cross-link DNA induced by tyrosinase and found that the o-quinone is key intermediate in the process by using the nucleophile 3-methyl-2-benzothiazolinone hydrazone (MBTH) in the tyrosinase assay. Their cytotoxicities to B16F1, Hela, and CHO cells were tested by MTT assays. The specific and potent abilities to kill the tyrosinase-efficient melanoma cells kindled our interest in exploring the relationship between their abilities of cross-linking DNA and their selective cytotoxicities to cells. Through an integrated approach including intracellular imaging for detection of the dihydroxyphenyl groups, alkaline comet assays, and γ-H2AX immunofluorescence assays, the speculation was confirmed. The bis(catechol) quaternary ammonium derivatives showed notable cell selectivity because they displayed cytotoxicities after being oxidized by tyrosinase, and they were able to target the DNA efficiently in the tyrosinase-efficient melanoma cells, forming both alkylated and cross-linked species.
Co-reporter:Liang Xu, Dan Zhang, Jing Huang, Minggang Deng, Ming Zhang and Xiang Zhou
Chemical Communications 2010 vol. 46(Issue 5) pp:743-745
Publication Date(Web):26 Nov 2009
DOI:10.1039/B918045A
A novel dinuclear ruthenium(II) complex with high fluorescent selectivity between DNA quadruplex structures and duplex structures was generated, and using an iodide-quenching strategy, G-quadruplex structures can be easily distinguished from duplex structures by the naked eye.
Co-reporter:Yuhao Du, Xiaocheng Weng, Jing Huang, Dan Zhang, Heng Ma, Dong Chen, Xiang Zhou, Jean-François Constant
Bioorganic & Medicinal Chemistry 2010 Volume 18(Issue 11) pp:4149-4153
Publication Date(Web):1 June 2010
DOI:10.1016/j.bmc.2009.11.026
Oligonucleotide-selenium conjugate was designed and synthesized and its sequence-specific cross-linking ability was investigated. The selenide derivatives can generate covalent interstrand cross-linking with its complementary strand through the formation of o-QM intermediate induced by periodate oxidation. A cross-linking reaction yield of up to 50% was obtained. Hydroxyl radical footprinting experiment revealed that the quinone appendage specifically alkylated the cytosine base extending the duplex formed between the conjugate and the target strand.Oligonucleotide-selenium conjugate was designed and synthesized and its sequence-specific cross-linking ability was investigated.
Co-reporter:Yuhao Du, Dan Zhang, Wei Chen, Ming Zhang, Yangyang Zhou, Xiang Zhou
Bioorganic & Medicinal Chemistry 2010 Volume 18(Issue 3) pp:1111-1116
Publication Date(Web):1 February 2010
DOI:10.1016/j.bmc.2009.12.049
One N-confused porphyrin derivative was prepared and its first observation that it could stabilize G-quadruplex and possessed high selectivity over duplex DNA was made, furthermore, it was also proved to possess the capacity to induce a structural transition from the antiparallel to the mixed-type hybrid G-quadruplex structure.One N-confused porphyrin derivative was prepared and its first observation that it could stabilize G-quadruplex and possessed high selectivity over duplex DNA was made.
Co-reporter:Heng Ma;Ming Zhang;Dan Zhang;Rong Huang;Yang Zhao;Hao Yang;Yijing Liu;Xiaocheng Weng Dr.;Yangyang Zhou;Minggang Deng Dr.;Liang Xu
Chemistry – An Asian Journal 2010 Volume 5( Issue 1) pp:114-122
Publication Date(Web):
DOI:10.1002/asia.200900270
Abstract
G-quadruplex DNA plays an important role in the potential therapeutic target for the design and development of anticancer drugs. As various G-quadruplex sequences in the promoter regions or telomeres can form different secondary structural modes and display a diversity of biology functions, variant G-quadruplex interactive agents may be necessary to cure different disease by differentiating variant types of G-quadruplexes. We synthesize five cationic methylpyridylium corroles and compare the interactions of corroles with different types of G-quadruplexes such as cmyc, htelo, and bcl2 by using surface plasmon resonance. Because of the importance of human telomere G-quadruplex DNA, we focus on the biological properties of the interactions between human telomere G-quadruplex DNA and corrole isomers using CD, Tm, PCR-stop (PCR= polymerase chain reaction), and polymerase-stop assay, which demonstrate the excellent ability of the corrole to induce and stabilize the G-quadruplex. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by a single group of methylpyridylium corrole isomers that may be optimized for potential selective cancer therapy.
Co-reporter:Xiaolin Wang;Jing Huang;Yangyang Zhou;Shengyong Yan;Xiaocheng Weng;Xiaojun Wu;Minggang Deng
Angewandte Chemie 2010 Volume 122( Issue 31) pp:5433-5437
Publication Date(Web):
DOI:10.1002/ange.201002290
Co-reporter:Xiaolin Wang;Jing Huang;Yangyang Zhou;Shengyong Yan;Xiaocheng Weng;Xiaojun Wu;Minggang Deng
Angewandte Chemie International Edition 2010 Volume 49( Issue 31) pp:5305-5309
Publication Date(Web):
DOI:10.1002/anie.201002290
Co-reporter:Jing Huang, Guorui Li, Zhiguo Wu, Zhibin Song, Yangyang Zhou, Liang Shuai, Xiaocheng Weng, Xiang Zhou and Guangfu Yang
Chemical Communications 2009 (Issue 8) pp:902-904
Publication Date(Web):22 Jan 2009
DOI:10.1039/B819789J
A bisbenzimidazole was discovered to bind helix DNA, while related benzobisimidazole derivatives were found to bind and induce different G-quadruplex isomers.
Co-reporter:Jing Huang, Ming Wang, Yangyang Zhou, Xiaocheng Weng, Liang Shuai, Xiang Zhou, Deqing Zhang
Bioorganic & Medicinal Chemistry 2009 Volume 17(Issue 22) pp:7743-7748
Publication Date(Web):15 November 2009
DOI:10.1016/j.bmc.2009.09.040
AIE molecule silole 1 could be used to detect G-quadruplex formation using an exonuclease I hydrolysis assay. This visual observation of G-quadruplexes has been successfully used in investigating multiple G-quadruplexes, including the one-stranded telomeric, c-myc, c-kit, VEGF G-quadruplexes, and a d(G4T4G4) inter-molecular G-quadruplex. The detection of G-quadruplex can be also applied to G-quadruplex isomers induced by small molecules.
Co-reporter:Li Shuai;Shaoru Wang;Lixia Zhang;Boqiao Fu
Chemistry & Biodiversity 2009 Volume 6( Issue 6) pp:827-837
Publication Date(Web):
DOI:10.1002/cbdv.200800083
Co-reporter:Lin Wu;Li Yang;Jing Huang;Lixia Zhang;Xiaocheng Weng;Xiaolian Zhang;Chao Shen;Congyi Zheng
Chemistry & Biodiversity 2009 Volume 6( Issue 7) pp:1066-1076
Publication Date(Web):
DOI:10.1002/cbdv.200800173
Abstract
A series of cationic ester porphyrins are much more cytotoxic to tumor cells than photofrin, meso-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP4), and cisplatin. The lowest IC50 value for SGC7901 is ca. 6 nMin vitro with irradiation. These porphyrins also exhibited the most potent photo-induced cytotoxicity without photobleaching. HeLa Cell apoptosis induced by cationic ester porphyrins after illumination was examined by flow cytometric analysis, staining assays with propidium iodide and annexin V FITC-PI, and further confirmed by observing morphological changes in the cells. The result of this study indicates that these cationic ester porphyrins may be applied in photodynamic therapy (PDT) in the future.
Co-reporter:Ming Zhang;Jing Huang;Minggang Deng Dr.;Xiaocheng Weng Dr.;Heng Ma
Chemistry – An Asian Journal 2009 Volume 4( Issue 9) pp:1420-1423
Publication Date(Web):
DOI:10.1002/asia.200900200
Co-reporter:Dan Zhang;Minggang Deng;Liang Xu;Yangyang Zhou;Jing Yuwen
Chemistry - A European Journal 2009 Volume 15( Issue 33) pp:8117-8120
Publication Date(Web):
DOI:10.1002/chem.200901268
Co-reporter:Baoping Zhai, Li Shuai, Li Yang, Xiaocheng Weng, Lin Wu, Shaoru Wang, Tian Tian, Xiaojun Wu, Xiang Zhou and Congyi Zheng
Bioconjugate Chemistry 2008 Volume 19(Issue 8) pp:1535
Publication Date(Web):July 30, 2008
DOI:10.1021/bc7004686
β-Octabromo-meso-tetra(4-carboxyl)phenyl porphyrin 6 and β-octaphenyl-meso-tetra(4-carboxyl)phenyl porphyrin 8 were synthesized and fully characterized by 1H NMR, UV, and HRMS. Their cytotoxicities to tumor cells were tested using MTT assays. One kind of tumor cell apoptosis induced by these anionic porphyrins under irradiation was examined by flow cytometric analysis. The inhibition of Topo I (Topoisomerase I) indicates that Topo I preferentially binds to the synthesized compounds, thus blocking the interaction between Topo I and DNA. The results implied that compounds 4, 6, and 8 are potential inhibitors to Topo I, which might be one of the important factors inducing apoptosis of tumor cells.
Co-reporter:Shaoru Wang, Qilong Wang, Yan Wang, Lin Liu, Xiaocheng Weng, Guorui Li, Xiaolian Zhang, Xiang Zhou
Bioorganic & Medicinal Chemistry Letters 2008 Volume 18(Issue 24) pp:6505-6508
Publication Date(Web):15 December 2008
DOI:10.1016/j.bmcl.2008.10.047
Three water soluble anthraquinone derivatives were designed and synthesized employing click chemistry to prepare novel and potent antitumor drugs. An MTT assay indicated that all compounds had significant inhibitory activity against BGC gastric cancer cells in vitro. Apoptosis induced by these compounds was observed by flow cytometry and laser confocal microscopy. Mechanistic analysis showed that these compounds induced the generation of several reactive oxygen species, the loss of mitochondrial membrane potential (Δψm), the transition of mitochondrial permeability, and the release of cytochrome C from the mitochondrion to cytoplasm. These results suggest that the anthraquinones might be potential lead compounds for the cancer chemotherapy.Three water soluble anthraquinone derivatives were synthesized via employing click chemistry and the mechanistic study of the apoptotic induction was conducted in this paper.
Co-reporter:Lin Wu;Peng Hu;Ying Xiao;Ming Zhang;Lixia Zhang;Xiaocheng Weng;Xiaojun Wu;Xiaoping Cao
Chemistry & Biodiversity 2008 Volume 5( Issue 1) pp:153-161
Publication Date(Web):
DOI:10.1002/cbdv.200890005
Abstract
A series of systematically modified porphyrin esters, compounds 1–6, with multiple, permanent positive charges introduced at the meso-positions via N-methylated 4-, 3-, or 2-pyridyl moieties, were prepared and characterized. Their singlet-oxygen production, CT-DNA-binding properties, and plasmid-DNA photocleavage propensities were determined spectroscopically and by gel electrophoresis, and compared to those of the known, fourfold-charged parent porphyrin 4,4′,4″,4′′′-porphyrin-5,10,15,20-tetrayltetrakis(1-methylpyridinium) (TMPyP4). Some interesting structure–activity relationships could be established to rationalize effects affecting DNA binding mode and cleavage ability.
Co-reporter:Boqiao Fu;Dan Zhang;Xiaocheng Weng Dr.;Ming Zhang;Heng Ma;Yuzhi Ma
Chemistry - A European Journal 2008 Volume 14( Issue 30) pp:9431-9441
Publication Date(Web):
DOI:10.1002/chem.200800835
Abstract
A series of pyridinium and quaternary ammonium copper corroles has been designed and synthesized. All new compounds have been fully characterized by NMR spectroscopy, high-resolution mass spectrometry, UV/Vis spectrscopy, and elemental analysis. Biochemical studies have indicated that all of these corrole derivatives can stabilize G-quadruplex structures, with corrole 4 being the most effective according to the results of circular dichroism (CD) melting experiments, polymerase chain reaction (PCR) stop assays, and surface plasmon resonance (SPR) experiments. Moreover, both corroles 3 and 4 tend to induce the human telomeric sequence to form hybrid G-quadruplex structures, whereas corroles 8 and 9 are more inclined to induce the human telomeric sequence to form antiparallel G-quadruplex structures.
Co-reporter:Zhibin Song;Xiaocheng Weng;Liwei Weng;Jing Huang;Xiaolin Wang;Minghui Bai;Yangyang Zhou;Guangfu Yang
Chemistry - A European Journal 2008 Volume 14( Issue 19) pp:5751-5754
Publication Date(Web):
DOI:10.1002/chem.200800783
Co-reporter:Li Yang, Feng Liang, Min Liu, Congyi Zheng, Shuhui Wan, Xiaoqin Xiong, Xiaolian Zhang, Chao Shen, Xiang Zhou
Bioorganic & Medicinal Chemistry Letters 2007 Volume 17(Issue 6) pp:1818-1822
Publication Date(Web):15 March 2007
DOI:10.1016/j.bmcl.2006.12.036
Preliminary pharmacological tests showed that 1,7-dimethyl-1,4,7,10-tetraazacyclododecane (DMC) had antitumor activity against HeLa and A549 cell lines in vitro. The HeLa cells apoptosis induced by DMC was examined by flow cytometric meter, and further confirmed by observing the morphological changes and DNA fragmentation. No observation of A549 cells induced apoptosis was observed by DMC.The first apoptosis induction on human cancer cell lines of free macrocyclic polyamines is presented.
Co-reporter:Tian Tian;Li-Xia Zhang;Yang Song;Yi Wang;Xiao-Cheng Weng
Chemistry & Biodiversity 2007 Volume 4(Issue 5) pp:947-954
Publication Date(Web):18 MAY 2007
DOI:10.1002/cbdv.200790084
A series of biphenol-derived quaternary ammonium salts, originally developed as DNA-cross-linking agents, and carrying either two (i.e., 1) or four (i.e., 2) net positive charges, were investigated for their in vitro DNA-transcription- and acetylcholinesterase (AChE)-inhibitory activities. The effects of charge and type of linker between the two phenolic residues were systematically investigated. Several compounds showed good activities in both tests, which makes them potential lead candidates for drug design.
Co-reporter:Xiao-Cheng Weng;Jing Huang;Li-Ge Ren;Song Wu;Li-Wei Weng;Shu-Gao Zhu
Chemistry & Biodiversity 2007 Volume 4(Issue 7) pp:1501-1507
Publication Date(Web):16 JUL 2007
DOI:10.1002/cbdv.200790129
A series of dicationic porphyrins were found to specifically recognize loop structures of oligodeoxynucleotides, and to selectively oxidize guanine residues upon photo-irradiation at micromolar concentrations. These compounds could, thus, be employed as promising structural probes for specific secondary DNA structures. The production of singlet oxygen (1O2) is responsible for the DNA-modification profiles. Both UV-titration and thermal-melting experiments indicate that the strong affinity of the charged porphyrins towards DNA loops is responsible for these molecular-recognition phenomena.
Co-reporter:Xiao-Cheng Weng;Jing Huang;Li-Ge Ren;Zhi-Bin Song;Xiao-Qin Xiong;An-Ming Zhang;Jin-Xi Li;Xiao-Ping Cao;Yan Zhou
Chemistry & Biodiversity 2007 Volume 4(Issue 2) pp:215-223
Publication Date(Web):20 FEB 2007
DOI:10.1002/cbdv.200790026
The interaction between CT-DNA and the zinc phthalocyanine ZnPc (1) was studied by UV/VIS and fluorescence titration, as well as by thermal denaturation. ZnPc was found to strongly bind to CT-DNA (Kapp=7.35×105 M−1) in a non-intercalative mode. The photosensitized cleavage of pBR322 DNA was found to efficiently proceed via singlet-oxygen (1O2) production. Further, ZnPc (1) caused site-specific scission of guanine (G) bases around the bulge of the hairpin oligonucleotides OD1–OD3, as clearly shown by gel-electrophoresis experiments.
Co-reporter:Xiaocheng Weng;Lige Ren;Liwei Weng;Jing Huang;Shugao Zhu ;Linhong Weng
Angewandte Chemie 2007 Volume 119(Issue 42) pp:
Publication Date(Web):13 SEP 2007
DOI:10.1002/ange.200700844
Auf DNA-Fang: Durch Oxidation mit Natriumperiodat oder Bestrahlung entstehen aus Phenylseleniden wie 1ortho-Chinonmethid-Intermediate, die Doppelstrang-DNA vernetzen. Die Kristallstrukturanalyse eines Derivats von 1 zeigt eine verdrehte Biphenyl-Einheit; diese Beobachtung könnte erklären, warum 1 effektiv mit dem DNA-Rückgrat wechselwirkt.
Co-reporter:Xiaocheng Weng;Lige Ren;Liwei Weng;Jing Huang;Shugao Zhu ;Linhong Weng
Angewandte Chemie International Edition 2007 Volume 46(Issue 42) pp:
Publication Date(Web):13 SEP 2007
DOI:10.1002/anie.200700844
Checking the traps: When a phenyl selenide compound such as 1 was oxidized with sodium periodate or irradiated, an ortho-quinone methide intermediate formed and reacted with a DNA duplex by cross-linking. In the crystal structure of a derivative of 1 the biphenyl unit is twisted, and this might explain how 1 can interact effectively with the DNA backbone.
Co-reporter:Lige Ren;Anming Zhang;Jing Huang;Ping Wang;Xiaocheng Weng;Lixia Zhang;Feng Liang Dr.;Zheng Tan Dr.
ChemBioChem 2007 Volume 8(Issue 7) pp:
Publication Date(Web):16 MAR 2007
DOI:10.1002/cbic.200600554
Water-soluble, octacationic zinc phthalocyanine (ZnPc) was found to be a very good G-quadruplex DNA stabilizer by using UV-melting studies and DNA polymerase stop assays, and a potent telomerase inhibitor by using the telomeric repeat amplification protocol (TRAP) assay. The compound’s DNA-binding properties were also studied by surface plasmon resonance (SPR). Furthermore, CD experiments demonstrated that ZnPc could induce intramolecular G-quadruplex structure transition from the antiparallel to parallel form. More importantly, ZnPc was found to induce parallel structure formation in cation-deficient conditions. The stability of the induced structure was determined with CD melting assays.
Co-reporter:Yang Song, Tian Tian, Ping Wang, Hanping He, Wulue Liu, Xiang Zhou, Xiaoping Cao, Xiao-Lian Zhang and Xin Zhou
Organic & Biomolecular Chemistry 2006 vol. 4(Issue 17) pp:3358-3366
Publication Date(Web):01 Aug 2006
DOI:10.1039/B604552A
We report here that phenol derivatives with two and four quaternary ammoniums were synthesized and their abilities to bind and cross-link DNA were investigated. Thermal denaturizing studies indicated that derivatives possess similar DNA binding abilities and gel electrophoresis revealed that more charges (series B) and electronic donation substitute linkers (like –S–) dramatically increase the DNA cross-linking abilities.
Co-reporter:Ping Wang;Lige Ren;Hanping He Dr.;Feng Liang Dr. Dr.;Zheng Tan Dr.
ChemBioChem 2006 Volume 7(Issue 8) pp:
Publication Date(Web):29 JUN 2006
DOI:10.1002/cbic.200600036
Not adding anything new? Phenol quaternary ammonium derivatives have been found to cross-link DNA efficiently. Experimental data indicate that a phenol quaternary ammonium cationic porphyrin (TQMP) potently inhibits a telomerase (IC50=1.7 μM) due to its selective, stabilizing interactions with G-quadruplexes. These interactions might derive from the greater flexibility of TQMP over pyridinium porphyrins and its steric effect.
Co-reporter:Tian Tian, Shuang Peng, Heng Xiao, Xiaoe Zhang, Shan Guo, Shaoru Wang, Xiang Zhou, Songmei Liu and Xin Zhou
Chemical Communications 2013 - vol. 49(Issue 26) pp:NaN2654-2654
Publication Date(Web):2013/02/11
DOI:10.1039/C3CC38818B
The present study demonstrated a highly sensitive strategy for measuring telomerase activity in cell extracts. Furthermore, we applied the new strategy for in situ detection of telomerase at the cellular level in cancer cells, together with a normal cell as the negative control.
Co-reporter:
Analytical Methods (2009-Present) 2014 - vol. 6(Issue 20) pp:
Publication Date(Web):
DOI:10.1039/C4AY01457J
In this study, we used the “cell-SELEX” strategy to generate four new aptamers with high binding affinity for Huh7.5.1. and HepG2 cells, as indicated by Kd values in the low nanomolar range, as well as high specificity compared to L-02 normal human liver cells. Moreover, the aptamers could distinguish human liver tumour tissues from normal tissues. Incorporation of the aptamer into probes permitted activation by target liver cancer cells to yield enhanced fluorescence and the detection of 103 orders of target liver cancer cells. The newly generated aptamers have great potential in early cancer diagnosis.
Co-reporter:Yuqi Chen, Tingting Hong, Shaoru Wang, Jing Mo, Tian Tian and Xiang Zhou
Chemical Society Reviews 2017 - vol. 46(Issue 10) pp:NaN2872-2872
Publication Date(Web):2017/03/29
DOI:10.1039/C6CS00599C
The epigenetic modification of nucleic acids represents one of the most significant areas of study in the field of nucleic acids because it makes gene regulation more complex and heredity more complicated, thus indicating its profound impact on aspects of heredity, growth, and diseases. The recent characterization of epigenetic modifications of DNA and RNA using chemical labelling strategies has promoted the discovery of these modifications, and the newly developed single-base or single-cell resolution mapping strategies have enabled large-scale epigenetic studies in eukaryotes. Due to these technological breakthroughs, several new epigenetic marks have been discovered that have greatly extended the scope and impact of epigenetic modifications in nucleic acids over the past few years. Because epigenetics is reversible and susceptible to environmental factors, it could potentially be a promising direction for clinical medicine research. In this review, we have comprehensively discussed how these epigenetic marks are involved in disease, including the pathogenesis, prevention, diagnosis and treatment of disease. These findings have revealed that the epigenetic modification of nucleic acids has considerable significance in various areas from methodology to clinical medicine and even in biomedical applications.
Co-reporter:Jinjun Wu, Heng Xiao, Tianlu Wang, Tingting Hong, Boshi Fu, Dongsheng Bai, Zhiyong He, Shuang Peng, Xiwen Xing, Jianlin Hu, Pu Guo and Xiang Zhou
Chemical Science (2010-Present) 2015 - vol. 6(Issue 5) pp:NaN3017-3017
Publication Date(Web):2015/03/11
DOI:10.1039/C5SC00484E
N
6-Methyladenosine (m6A) represents a relatively abundant modification in eukaryotic RNA. Because m6A has similar properties to adenosine and a low reactivity, limited research has been focused on this nucleoside. In this study, we revealed an important intermediate in the oxidation of m6A through the bicarbonate-activated peroxide system. Over the course of oxidation, we found a new mechanism in which N6-hydroxymethyladenosine (hm6A), N6-formyladenosine (f6A) and N6-hydroperoxymethyladenosine (oxm6A) were intermediate products, and adenosine was the final product. In this study, oxm6A was isolated using HPLC and characterized by mass spectrometry, NMR and diphenyl-1-pyrenylphosphine (DPPP) fluorescence detection. This study provides a new modified nucleoside and demonstrates oxidative demethylation of m6A by reactive oxygen species at the nucleobase level and in RNA strands.
Co-reporter:Boshi Fu, Jinguo Huang, Yuqi Chen, Yafen Wang, Tianrui Xue, GuoHua Xu, Shaoru Wang and Xiang Zhou
Chemical Communications 2016 - vol. 52(Issue 65) pp:NaN10055-10055
Publication Date(Web):2016/07/14
DOI:10.1039/C6CC04866H
Herein, we report two distinct G-quadruplex conformations of the same G-rich oligonucleotide, regulated by a small molecule. This is the first report in which both right- and left-handed G-quadruplex conformations have been obtained from the same sequence. We discriminated these two distinct conformations and investigated their kinetics and thermodynamics.
Co-reporter:Boshi Fu, Jinguo Huang, Dongsheng Bai, Yalun Xie, Yang Wang, Shaoru Wang and Xiang Zhou
Chemical Communications 2015 - vol. 51(Issue 95) pp:NaN16963-16963
Publication Date(Web):2015/09/24
DOI:10.1039/C5CC04784F
A label-free and biocompatible pH sensor system based on the aggregation-caused quenching (ACQ) probe has been reported herein. The DNA i-motif, a kind of pH-triggered structure, affects the aggregation of PTCDI derivatives by structural switch that would provide significant fluorescence signals responding to the different pH values. Our method not only shows sensitive and reversible response to pH changes, but also could expand the detection range by allosteric control of the DNA i-motif.
Co-reporter:Tingting Hong, Yushu Yuan, Tianlu Wang, Jingwei Ma, Qian Yao, Xiaoluan Hua, Yu Xia and Xiang Zhou
Chemical Science (2010-Present) 2017 - vol. 8(Issue 1) pp:NaN205-205
Publication Date(Web):2016/08/10
DOI:10.1039/C6SC02271E
N6-methyladenine (6mA) is reported as a potential epigenetic marker in eukaryotic genomes. However, accurate identification of the location of 6mA in DNA remains a challenging task. Here, we show that Ag+ can selectively stabilize the A–C mismatch and efficiently promote primer extension. In contrast, the complex of 6mA–Ag+–C is instable and therefore cannot be recognized by DNA polymerases, resulting in the termination of primer extension. Based on this finding, we successfully identified and quantified 6mA at the single-base level through the analysis of gel bands of extended primers and fluorescence measurements combined with rolling circle amplification. The high selectivity and sensitivity of this strategy may provide a new platform for the efficient analysis of 6mA in DNA in the future.
Co-reporter:
Analytical Methods (2009-Present) 2013 - vol. 5(Issue 15) pp:
Publication Date(Web):
DOI:10.1039/C3AY40581H
Based on graphene oxide and Hoechst 33258, bioassays towards target DNA and several enzymes including Exo III and Dam MTase were established. This strategy eliminates the need for modification of oligonucleotides, and can give similarly satisfactory results compared to traditional methods using labelled DNA. Moreover, “AND” and “INHIBIT” dual-output DNA logic gates were developed.
Co-reporter:
Analytical Methods (2009-Present) 2012 - vol. 4(Issue 7) pp:
Publication Date(Web):
DOI:10.1039/C2AY25362C
Sensitive and selective techniques for both Ag+ and Cys detection have been designed based on graphene oxide (GO) and G-quadruplex DNA. The G-quadruplex structure can capture the fluorescent molecule acridine orange (AO) from the surface of graphene oxide (GO), which will recover the fluorescence of AO that was initially quenched by GO. Then the addition of Ag+ will release AO back to GO, because Ag+ can destroy the G-quadruplex structure, giving a fluorescence quenching process again. Based on this “turn off” principle, a highly sensitive and selective Ag+ detection method was developed. In addition, cysteine (Cys) can capture Ag+ from the guanine base of DNA which will result in the regeneration of the G-quadruplex DNA structure and thus the regeneration of the fluorescence signal. This “turn on” principle can be used for the development of a highly selective and sensitive detection method for Cys.
Co-reporter:Chen Xu, Jinjun Wu, Wenting Liu, Tingting Hong, Tianlu Wang, Xiaoe Zhang, Boshi Fu, Fan Wu, Zhiguo Wu and Xiang Zhou
Chemical Communications 2016 - vol. 52(Issue 41) pp:NaN6836-6836
Publication Date(Web):2016/04/22
DOI:10.1039/C6CC03138B
We present here a novel and efficient method for 5mC detection using a DNA strand exchange reaction (SER) strategy. This enzyme-free method needs no pre-treatment of target DNAs and can be adapted to most of the target duplexes under physiological conditions. The high sequence selectivity of this method can distinguish 5mC from normal cytosine in an accurate manner.
Co-reporter:Zhiyong He, Yuqi Chen, Yafen Wang, Jiaqi Wang, Jing Mo, Boshi Fu, Zijing Wang, Yuhao Du and Xiang Zhou
Chemical Communications 2016 - vol. 52(Issue 55) pp:NaN8548-8548
Publication Date(Web):2016/06/10
DOI:10.1039/C6CC03098J
A new DNA building block (dTetU) bearing a tetrazole and allyloxy group at N-phenyl ring linked through an aminopropynyl linker to the 5-position of 2′-deoxyuridine was synthesized. The modified DNA can be lit up via a photoinduced intramolecular tetrazole–alkene cycloaddition reaction, but quenched when the fully-matched double strand is formed. This conspicuous difference in fluorescence could open a door for DNA single nucleotide polymorphism (SNP) typing.
Co-reporter:Yuqi Chen, Yanyan Song, Fan Wu, Wenting Liu, Boshi Fu, Bingkun Feng and Xiang Zhou
Chemical Communications 2015 - vol. 51(Issue 32) pp:NaN6983-6983
Publication Date(Web):2015/03/10
DOI:10.1039/C5CC01389E
A conveniently amplified DNA AND logic gate platform was designed for the highly sensitive detection of low-abundance DNA fragment inputs based on strand displacement reaction and rolling circle amplification strategy. Compared with others, this system can detect miRNAs in biological samples. The success of this strategy demonstrates the potential of DNA logic gates in disease diagnosis.
Co-reporter:Tian Tian, Xiaoe Zhang, Boshi Fu, Yuelin Long, Shuang Peng, Shaoru Wang, Xiang Zhou and Xin Zhou
Chemical Communications 2013 - vol. 49(Issue 85) pp:NaN9970-9970
Publication Date(Web):2013/08/20
DOI:10.1039/C3CC45423A
We have conducted the first systematic investigation of DNAs with modified cytosines, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), under hot alkali treatment.
Co-reporter:Tian Tian, Shuang Peng, Heng Xiao, Yuelin Long, Boshi Fu, Xiaoe Zhang, Shan Guo, Shaoru Wang, Xiang Zhou, Songmei Liu and Xin Zhou
Chemical Communications 2013 - vol. 49(Issue 86) pp:NaN10087-10087
Publication Date(Web):2013/09/05
DOI:10.1039/C3CC44017F
Here, we first demonstrated that 5-MedCTP could be incorporated into the synthetic DNA template by the exonuclease deficient Klenow fragment with a much higher efficiency than dCTP and 5-hydroxymethyl-dCTP. Further, we first conducted a comparable study of primer extension reaction using templates containing deoxycytidine (dC) or 5-methyldeoxycytidine (5-mdC) for incorporating different triphosphates. Based on our findings, 5-methyldeoxycytidine could enhance the substrate activity of the Klenow fragment (exo-) and this feature could potentially be used in DNA methylation analysis.
Co-reporter:Tingting Hong, Tianlu Wang, Zhiyong He, Jingwei Ma, Heng Xiao, Jinguo Huang, Wuxiang Mao and Xiang Zhou
Chemical Communications 2014 - vol. 50(Issue 50) pp:NaN6655-6655
Publication Date(Web):2014/05/02
DOI:10.1039/C4CC01933D
The methylation status of each CpG site can be monitored by Fl-dGTP incorporated asymmetric PCR assay. The ability of quantitative detection makes it a good choice for detecting partial methylation at CpG sites compared with others. And the monitoring is not limited to sites within PCR primers or restriction enzyme-recognition sites.
Co-reporter:Tian Tian, Heng Xiao, Xiaolian Zhang, Shuang Peng, Xiaoe Zhang, Shan Guo, Shaoru Wang, Songmei Liu, Xin Zhou, Craig Meyers and Xiang Zhou
Chemical Communications 2013 - vol. 49(Issue 1) pp:NaN77-77
Publication Date(Web):2012/11/05
DOI:10.1039/C2CC36728A
We reported an efficient strategy based on a strand displacement amplification for serum miRNA detection. In such a system, a multiplexed, sensitive and quick detection of miRNAs could be achieved through a combination of fluorescence labeled probes, a common primer and a polymerase. This could be potentially used in the clinical field to achieve early disease diagnosis and prognosis.
Co-reporter:Shaoru Wang, Boshi Fu, Shuang Peng, Xiaoe Zhang, Tian Tian and Xiang Zhou
Chemical Communications 2013 - vol. 49(Issue 72) pp:NaN7922-7922
Publication Date(Web):2013/06/26
DOI:10.1039/C3CC44075C
This study is the first to investigate the interactions of hemin with a G-triplex DNA of T1 using different DNA binding assays. The low intrinsic peroxidatic activity of hemin could be significantly enhanced using T1. Furthermore, much decreased oxidation enhancement by T2 or T3 with one key guanine mutation was observed, and the observed peroxidatic activity of T1 should be directly due to the G-triplex complexed with hemin.
Co-reporter:Liang Xu, Dan Zhang, Jing Huang, Minggang Deng, Ming Zhang and Xiang Zhou
Chemical Communications 2010 - vol. 46(Issue 5) pp:NaN745-745
Publication Date(Web):2009/11/26
DOI:10.1039/B918045A
A novel dinuclear ruthenium(II) complex with high fluorescent selectivity between DNA quadruplex structures and duplex structures was generated, and using an iodide-quenching strategy, G-quadruplex structures can be easily distinguished from duplex structures by the naked eye.
Co-reporter:Jing Huang, Guorui Li, Zhiguo Wu, Zhibin Song, Yangyang Zhou, Liang Shuai, Xiaocheng Weng, Xiang Zhou and Guangfu Yang
Chemical Communications 2009(Issue 8) pp:NaN904-904
Publication Date(Web):2009/01/22
DOI:10.1039/B819789J
A bisbenzimidazole was discovered to bind helix DNA, while related benzobisimidazole derivatives were found to bind and induce different G-quadruplex isomers.
Co-reporter:Tian Tian, Heng Xiao, Yuelin Long, Xiaoe Zhang, Shaoru Wang, Xiang Zhou, Songmei Liu and Xin Zhou
Chemical Communications 2012 - vol. 48(Issue 80) pp:NaN10033-10033
Publication Date(Web):2012/08/23
DOI:10.1039/C2CC35648A
The analysis of DNA methylation and MTase (methyltransferase) activity is important in epigenetic study. We have developed a novel strategy for sensitive analysis of MTase activity based on a hairpin shaped DNAzyme; 8–17 DNAzyme amplicon has been adopted and found to be very effective in such analysis.
Co-reporter:Liang Xu, Shuo Feng and Xiang Zhou
Chemical Communications 2011 - vol. 47(Issue 12) pp:NaN3519-3519
Publication Date(Web):2011/02/10
DOI:10.1039/C0CC05242F
We provide a novel insight into dynamic conversion of the human telomeric G-quadruplexes and particularly a step-to-step transformation pathway of the long sequence containing two quadruplex units in K+ solution in a molecular crowding environment, implying a possible behavior of the human telomeric DNA under physiological conditions.
Co-reporter:Shengyong Yan, Rong Huang, Yangyang Zhou, Ming Zhang, Minggang Deng, Xiaolin Wang, Xiaocheng Weng and Xiang Zhou
Chemical Communications 2011 - vol. 47(Issue 4) pp:NaN1275-1275
Publication Date(Web):2010/11/22
DOI:10.1039/C0CC02792H
In this thrombin detection system, the bright fluorescence of TASPI is almost eliminated by the DNA aptamer TBA (turn-off); however, in the presence of thrombin, it specifically binds to TBA by folding unrestricted TBA into an anti-parallel G-quadruplex structure and then releasing TASPI molecules, resulting in vivid and facile fluorescence recovery (turn-on).
Co-reporter:Chaoxing Liu;Yafen Wang;Xiong Zhang;Fan Wu;Wei Yang;Guangrong Zou;Qian Yao;Jiaqi Wang;Yuqi Chen;Shaoru Wang
Chemical Science (2010-Present) 2017 - vol. 8(Issue 6) pp:
Publication Date(Web):2017/05/30
DOI:10.1039/C7SC00637C
Recently, the detection of natural thymine modified 5-formyluracil has attracted widespread attention. Herein, we introduce a new insight into designing reagents for both the selective biotin enrichment and fluorogenic labelling of 5-formyluracil in DNA. Biotinylated o-phenylenediamine directly tethered to naphthalimide can switch on 5-formyluracil, under physiological conditions, which can then be used in cell imaging after exposure to γ-irradiation. In addition, its labelling property caused the polymerase extension to stop in the 5-formyluracil site, which gave us more information than the fluorescence did itself. The idea of detecting 5-formyluracil might be used in the synthesis of other modified diaminofluoresceins.
Co-reporter:Shaoru Wang, Jiaqi Wang, Xiaoe Zhang, Boshi Fu, Yanyan Song, Pei Ma, Kai Gu, Xin Zhou, Xiaolian Zhang, Tian Tian and Xiang Zhou
Chemical Science (2010-Present) 2016 - vol. 7(Issue 2) pp:NaN1446-1446
Publication Date(Web):2015/11/17
DOI:10.1039/C5SC02902C
N
6-Methyladenine (m6A) is the most abundant internal modification on mammalian mRNA. Very recently, m6A has been reported as a potentially important ‘epigenetic’ mark in eukaryotes. Until now, site-specific detection of m6A is technically very challenging. Here, we first reveal that m6A significantly hinders DNA- and RNA-directed DNA synthesis. Systematic investigations of 5′-triphosphates of a variety of 5-substituted 2′-deoxyuridine analogs in primer extension have been performed. In the current study, a quantitative analysis of m6A in the RNA or DNA context has been achieved, using Bst DNA polymerase catalyzed primer extension. Molecular dynamics study predicted that m6A in template tends to enter into and be restrained in the MGR region of Bst DNA polymerase, reducing conformational flexibility of the DNA backbone. More importantly, a site-specific determination of m6A in human ribosomal RNA (rRNA) with high accuracy has been afforded. Through a cumulative analysis of methylation alterations, we first reveal that significantly cancer-related changes in human rRNA methylation were present in patients with hepatocellular carcinoma.
Co-reporter:Tian Tian, Jiaqi Wang and Xiang Zhou
Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 8) pp:NaN2238-2238
Publication Date(Web):2014/12/16
DOI:10.1039/C4OB02104E
MicroRNA (miRNA) detection is of considerable significance in both disease diagnosis and in the study of miRNA function. The importance of miRNA itself is due to the complicated regulatory functions it plays in various life processes and its close relationship with some diseases. Traditional methods for miRNA detection do not meet the current demands, so various novel methods have been developed with a special focus on sensitivity and specificity. Herein, we summarize and discuss the newly developed miRNA detection methods.
Co-reporter:Jiaqi Wang, Shaoru Wang, Cheng Zhong, Tian Tian and Xiang Zhou
Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 34) pp:NaN8999-8999
Publication Date(Web):2015/07/28
DOI:10.1039/C5OB01340B
Here, we have provided novel insights into the effects of 8-oxodG substitutions on B–Z transitions of CpG dinucleotide DNAs. A combination of different techniques including a CD study, a PAGE analysis, DFT calculations and molecular modeling has been collectively used.
Co-reporter:Xiwen Xing, Xiaolin Wang, Liang Xu, Yang Tai, Luyang Dai, Xiaolong Zheng, Wuxiang Mao, Xiaowei Xu and Xiang Zhou
Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 15) pp:NaN4613-4613
Publication Date(Web):2015/03/19
DOI:10.1039/C5OB90054A
Correction for ‘Light-driven conformational regulation of human telomeric G-quadruplex DNA in physiological conditions’ by Xiwen Xing et al., Org. Biomol. Chem., 2011, 9, 6639–6645.
Co-reporter:Xiwen Xing, Xiaoling Wang, Liang Xu, Yang Tai, Luyang Dai, Xiaolong Zheng, Wuxiang Mao, Xiaowei Xu and Xiang Zhou
Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 19) pp:NaN6645-6645
Publication Date(Web):2011/06/27
DOI:10.1039/C1OB05939D
Human telomeric G-quadruplexes have raised broad interest not just due to their involvement in the regulation of gene expressions and telomerase activities but also because of their application in nanoarchitectures. Herein, three azobenzene derivatives 1–3 were synthesized with different substituent groups and their photo-isomerization properties were investigated by UV/Vis spectroscopy. Then circular dichroism spectroscopy (CD), fluorescence experiments and native-gel electrophoresis were performed to evaluate their capabilities of conformational photo-regulation both in the absence and presence of metal ions. The results suggested that the compounds synthesized can successfully regulate the conformation of human telomeric G-quadruplex DNA in K+ conditions to some extent. This work will initiate the possibility for the design and intriguing application of light-induced switching to photoregulate the conformation of G-quadruplex DNA under physiological conditions, providing a possible pathway to control G-quadruplex conformation in biological applications and also expanding the potential use of G-quadruplexes in nanomachines.
Co-reporter:Jun Wu, Rong Huang, Changcheng Wang, Wenting Liu, Jiaqi Wang, Xiaocheng Weng, Tian Tian and Xiang Zhou
Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 4) pp:NaN585-585
Publication Date(Web):2012/11/02
DOI:10.1039/C2OB26680F
A new bifunctional compound NCC, which undergoes thiol-mediated disulfide cleavage after cell entry, produces a red-shifted fluorescent emission in the cytosol and releases free active DNA alkylating agent CLB into the nucleus, and finally leads to DNA damage and cell death.
Co-reporter:Pu Guo, Xiaowei Xu, Xiaoyu Qiu, Yimin Zhou, Shengyong Yan, Changcheng Wang, Chunjiang Lu, Wen Ma, Xiaocheng Weng, Xianzheng Zhang and Xiang Zhou
Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 10) pp:NaN1613-1613
Publication Date(Web):2013/01/22
DOI:10.1039/C3OB27519A
Fluorescent nucleosides (dUbmz) with desirable fluorescence quantum yield (Φ) are synthesized from almost non-fluorescent 5-fdU and o-phenylenediamine derivatives. The fluorescence of these nucleosides is quite sensitive to pH and organic solvents. 4-Methoxybenzene-1,2-diamine was used for the detection of 5-fdU among natural nucleosides.
Co-reporter:Jun Wu, Rong Huang, Tianlu Wang, Xi Zhao, Wanyi Zhang, Xiaocheng Weng, Tian Tian and Xiang Zhou
Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 14) pp:NaN2369-2369
Publication Date(Web):2013/01/04
DOI:10.1039/C2OB27324A
Two new small compounds, which undergo fluoride-mediated self rearrangement, produce active DNA alkylating agent nitrogen mustard leading to DNA damage and finally cell death, providing potential antitumor prodrugs.
Co-reporter:Wuxiang Mao, Jianlin Hu, Tingting Hong, Xiwen Xing, Sen Wang, Xi Chen and Xiang Zhou
Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 21) pp:NaN3572-3572
Publication Date(Web):2013/03/27
DOI:10.1039/C3OB40447A
Treatment of DNA containing 5-formylcytosine with hot piperidine produced a cleaved band at the position of 5-formylcytosine in DNA sequences. After oxidation with KRuO4, 5-hydroxymethylcytosine could also be detected using the same method. Using our strategy, we could detect 5-hydroxymethylcytosine and 5-formylcytosine respectively.