Yuan GUO

Find an error

Name:

Organization: University of Leeds , England

Department:

Title: (PhD)

Chemicals
References

Dissecting Multivalent Lectin–Carbohydrate Recognition Using Polyvalent Multifunctional Glycan-Quantum Dots

Co-reporter:Yuan Guo, Inga Nehlmeier, Emma Poole, Chadamas Sakonsinsiri, Nicole Hondow, Andy Brown, Qing Li, Shuang Li, Jessie Whitworth, Zhongjun Li, Anchi Yu, Rik Brydson, W. Bruce Turnbull, Stefan Pöhlmann, and Dejian Zhou

Journal of the American Chemical Society August 30, 2017 Volume 139(Issue 34) pp:11833-11833

Publication Date(Web):August 8, 2017

DOI:10.1021/jacs.7b05104

Multivalent protein–carbohydrate interactions initiate the first contacts between virus/bacteria and target cells, which ultimately lead to infection. Understanding the structures and binding modes involved is vital to the design of specific, potent multivalent inhibitors. However, the lack of structural information on such flexible, complex, and multimeric cell surface membrane proteins has often hampered such endeavors. Herein, we report that quantum dots (QDs) displayed with a dense array of mono-/disaccharides are powerful probes for multivalent protein–glycan interactions. Using a pair of closely related tetrameric lectins, DC-SIGN and DC-SIGNR, which bind to the HIV and Ebola virus glycoproteins (EBOV-GP) to augment viral entry and infect target cells, we show that such QDs efficiently dissect the different DC-SIGN/R-glycan binding modes (tetra-/di-/monovalent) through a combination of multimodal readouts: Förster resonance energy transfer (FRET), hydrodynamic size measurement, and transmission electron microscopy imaging. We also report a new QD-FRET method for quantifying QD-DC-SIGN/R binding affinity, revealing that DC-SIGN binds to the QD >100-fold tighter than does DC-SIGNR. This result is consistent with DC-SIGN’s higher trans-infection efficiency of some HIV strains over DC-SIGNR. Finally, we show that the QDs potently inhibit DC-SIGN-mediated enhancement of EBOV-GP-driven transduction of target cells with IC50 values down to 0.7 nM, matching well to their DC-SIGN binding constant (apparent Kd = 0.6 nM) measured by FRET. These results suggest that the glycan-QDs are powerful multifunctional probes for dissecting multivalent protein–ligand recognition and predicting glyconanoparticle inhibition of virus infection at the cellular level.

Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent ProteinLigand Interactions

Co-reporter:Dr. Yuan Guo;Chadamas Sakonsinsiri;Dr. Inga Nehlmeier;Dr. Martin A. Fascione;Dr. Haiyan Zhang;Weili Wang;Dr. Stefan Pöhlmann;Dr. W. Bruce Turnbull;Dr. Dejian Zhou

Angewandte Chemie International Edition 2016 Volume 55( Issue 15) pp:4738-4742

Publication Date(Web):

DOI:10.1002/anie.201600593

Abstract

A highly efficient cap-exchange approach for preparing compact, dense polyvalent mannose-capped quantum dots (QDs) has been developed. The resulting QDs have been successfully used to probe multivalent interactions of HIV/Ebola receptors DC-SIGN and DC-SIGNR (collectively termed as DC-SIGN/R) using a sensitive, ratiometric Förster resonance energy transfer (FRET) assay. The QD probes specifically bind DC-SIGN, but not its closely related receptor DC-SIGNR, which is further confirmed by its specific blocking of DC-SIGN engagement with the Ebola virus glycoprotein. Tuning the QD surface mannose valency reveals that DC-SIGN binds more efficiently to densely packed mannosides. A FRET-based thermodynamic study reveals that the binding is enthalpy-driven. This work establishes QD FRET as a rapid, sensitive technique for probing structure and thermodynamics of multivalent protein–ligand interactions.

Back Cover: Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent ProteinLigand Interactions (Angew. Chem. Int. Ed. 15/2016)

Co-reporter:Dr. Yuan Guo;Chadamas Sakonsinsiri;Dr. Inga Nehlmeier;Dr. Martin A. Fascione;Dr. Haiyan Zhang;Weili Wang;Dr. Stefan Pöhlmann;Dr. W. Bruce Turnbull;Dr. Dejian Zhou

Angewandte Chemie International Edition 2016 Volume 55( Issue 15) pp:

Publication Date(Web):

DOI:10.1002/anie.201602014

Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent ProteinLigand Interactions

Co-reporter:Dr. Yuan Guo;Chadamas Sakonsinsiri;Dr. Inga Nehlmeier;Dr. Martin A. Fascione;Dr. Haiyan Zhang;Weili Wang;Dr. Stefan Pöhlmann;Dr. W. Bruce Turnbull;Dr. Dejian Zhou

Angewandte Chemie 2016 Volume 128( Issue 15) pp:4816-4820

Publication Date(Web):

DOI:10.1002/ange.201600593

Abstract

Rcktitelbild: Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent ProteinLigand Interactions (Angew. Chem. 15/2016)

Co-reporter:Dr. Yuan Guo;Chadamas Sakonsinsiri;Dr. Inga Nehlmeier;Dr. Martin A. Fascione;Dr. Haiyan Zhang;Weili Wang;Dr. Stefan Pöhlmann;Dr. W. Bruce Turnbull;Dr. Dejian Zhou

Angewandte Chemie 2016 Volume 128( Issue 15) pp:

Publication Date(Web):

DOI:10.1002/ange.201602014

Robust and specific ratiometric biosensing using a copper-free clicked quantum dot–DNA aptamer sensor

Co-reporter:Haiyan Zhang, Guoqiang Feng, Yuan Guo and Dejian Zhou

Nanoscale 2013 vol. 5(Issue 21) pp:10307-10315

Publication Date(Web):15 Aug 2013

DOI:10.1039/C3NR02897F

We report herein the successful preparation of a compact and functional CdSe–ZnS core–shell quantum dot (QD)–DNA conjugate via highly efficient copper-free “click chemistry” (CFCC) between a dihydro-lipoic acid–polyethylene glycol–azide (DHLA–PEG–N3) capped QD and a cyclooctyne modified DNA. This represents an excellent balance between the requirements of high sensitivity, robustness and specificity for the QD-FRET (Förster resonance energy transfer) based sensor as confirmed by a detailed FRET analysis on the QD–DNA conjugate, yielding a relatively short donor–acceptor distance of ∼5.8 nm. We show that this CFCC clicked QD–DNA conjugate is not only able to retain the native fluorescence quantum yield (QY) of the parent DHLA–PEG–N3 capped QD, but also well-suited for robust and specific biosensing; it can directly quantitate, at the pM level, both labelled and unlabelled complementary DNA probes with a good SNP (single-nucleotide polymorphism) discrimination ability in complex media, e.g. 10% human serum via target-binding induced FRET changes between the QD donor and the dye acceptor. Furthermore, this sensor has also been successfully exploited for the detection, at the pM level, of a specific protein target (thrombin) via the encoded anti-thrombin aptamer sequence in the QD–DNA conjugate.

Ultrasensitive single-nucleotide polymorphism detection using target-recycled ligation, strand displacement and enzymatic amplification

Co-reporter:Yue Zhang, Yuan Guo, Philip Quirke and Dejian Zhou

Nanoscale 2013 vol. 5(Issue 11) pp:5027-5035

Publication Date(Web):10 Apr 2013

DOI:10.1039/C3NR01010D

We report herein the development of a highly sensitive and selective approach for label-free DNA detection by combining target-recycled ligation (TRL), magnetic nanoparticle assisted target capture/separation, and efficient enzymatic amplification. We show that our approach can detect as little as 30 amol (600 fM in 50 μL) of unlabelled single-stranded DNA targets and offer an exquisitely high discrimination ratio (up to >380 fold with background correction) between a perfect-match cancer mutant and its single-base mismatch (wild-type) DNA target. Furthermore, it can quantitate the rare cancer mutant (KRAS codon 12) in a large excess of coexisting wild-type DNAs down to 0.75%. This sensor appears to be well-suited for sensitive SNP detection and a wide range of DNA mutation based diagnostic applications.

Sensitive, Simultaneous Quantitation of Two Unlabeled DNA Targets Using a Magnetic Nanoparticle–Enzyme Sandwich Assay

Co-reporter:Yue Zhang, Chalermchai Pilapong, Yuan Guo, Zhenlian Ling, Oscar Cespedes, Philip Quirke, and Dejian Zhou

Analytical Chemistry 2013 Volume 85(Issue 19) pp:9238

Publication Date(Web):August 26, 2013

DOI:10.1021/ac402081u

We report herein the development of a simple, sensitive colorimetric magnetic nanoparticle (MNP)–enzyme-based DNA sandwich assay that is suitable for simultaneous, label-free quantitation of two DNA targets down to 50 fM level. It can also effectively discriminate single-nucleotide polymorphisms (SNPs) in genes associated with human cancers (KRAS codon 12/13 SNPs). This assay uses a pair of specific DNA probes, one being covalently conjugated to an MNP for target capture and the other being linked to an enzyme for signal amplification, to sandwich a DNA target, allowing for convenient magnetic separation and subsequent efficient enzymatic signal amplification for high sensitivity. Careful optimization of the MNP surfaces and assay conditions greatly reduced the background, allowing for sensitive, specific detection of as little as 5 amol (50 fM in 100 μL) of target DNA. Moreover, this sensor is robust, it can effectively discriminate cancer-specific SNPs against the wild-type noncancer target, and it works efficiently in 10% human serum. Furthermore, this sensor can simultaneously quantitate two different DNA targets by using two pairs of unique capture- and signal-DNA probes specific for each target. This general, simple, and sensitive DNA sensor appears to be well-suited for a wide range of genetics-based biosensing and diagnostic applications.