•D2-like and 5-HT2A receptors were modeled using β2-adrenergic receptor as template.•Homology model refined by molecular dynamics simulations.•Docking studies show the correlation between computed and experimental pKi is good.•Evidenced D3R model is reliable by comparing modeled D3R with crystal structure.•These models will be useful in virtual screening and design of antipsychotic drugs.Psychiatric disorders, such as schizophrenia, bipolar disorder and major depression, are paid more and more attention by human due to their upward tendency in modern society. D2-like and 5-HT2A receptors have been proposed as targets of antipsychotic drugs. Atypical antipsychotic drugs have been deemed to improve the treatment of positive, negative and extrapyramidal symptoms. Unfortunately, no experimental structures for these receptors are available except D3 receptor (D3R). Therefore, it is necessary to construct structures of D2-like and 5-HT2A receptors to investigate the interaction between these receptors and their antagonists. Accordingly, homology models of dopamine D2, D3, D4 and serotonin 5-HT2A receptors have been built on the high-resolution crystal structure of the β2-adrenergic receptor, and refined by molecular dynamics simulations. The backbone root-mean-square deviation (RMSD) of D3R model relative to crystal structure is 1.3 Å, which proves the reliability of homology modeling. Docking studies reveal that the binding modes of four homology models and their antagonists are consistent with experimental site-directed mutagenesis data. The calculated pKi values agree well with the experimental pKi ones. Antagonists with linear structures such as butyrophenones and benzisoxazolyl piperidines are easily docked into D2-like and 5-HT2A receptors. Polycyclic aromatic compounds have weaker affinity with four receptors. Homology models of D2-like and 5-HT2A receptors will be helpful for predicting the affinity of novel ligands, and could be used as three-dimensional (3D) templates for antipsychotic virtual screening and further drug discovery.D2, D3, D4 and 5-HT2A receptors were modeled and refined by molecular dynamics simulations. Docking studies show the correlations between computed and experimental pKi is matched well. The homology models can be used as 3D templates for antipsychotic drug design and virtual screening in the future.

Diesters and diols were successfully converted into aliphatic polyesters by enzymatic lipase Candida sp.99-125 catalysis, with β-cyclodextrin acting as supporting architecture (in a similar way as chaperone proteins). No organic solvents were used. The polytransesterification was a much greener process, being solvent-free and without metal residues. Lipase Candida sp.99-125 showed a high catalytic activity for bulkpolymerization of diesters and diols with various numbers of methylene groups in their chains. β-Cyclodextrin encircled the linear polymer chain and maintained the chain in a proper configuration to avoid its coagulation. Lipase initiated the polymerization and β-cyclodextrin threaded onto the polymer chain to control the structure for producing high molecular weight polyesters. From a combination of diesters and diols, polyesters with a high molecular weight of 62,100 Da were obtained at 70 °C. The corresponding polyesters showed an excellent thermal stability till 350 °C and had a strong ability to crystallize with up to 72% crystallinity, contributing to their high storage modulus.Highlights► Aliphatic polyesters are synthesized by enzymatic lipase catalysis, without using solvents. ► Lipase from Candida sp. initiates the polymerization. ► β-Cyclodextrin safeguards the polymer chain from coagulation. ► High molecular weight polyesters (62,100 Da) are obtained in a three-stage reaction. ► Polymers are stable till 350 °C, with a 72% crystallinity, thus improving the storage modulus.

A mutant Xanthomonasmaltophilia BT-112 with high α-anomer-selective glycosylation activity was screened by a series of mutation methods including UV light, N-methyl-N-nitro-N-nitroso-guanidine treatment and quick neutron mutation. The α-arbutin titer increased 15-folds compared with the parent strain. The optimal conditions for culture medium and the operational conditions for lab-scale fermenter were investigated. Under optimized conditions, the maximal hydroquinone (HQ) tolerance of cells and yield of α-arbutin were 120 mM and 30.6 g/l, respectively. The molar conversion yield of α-arbutin based on the amount of HQ supplied reached 93.6 %. The product was identified as α-arbutin by 13C NMR and 1H NMR analysis. In conclusion, the results in this work provide a one-step and cost-effective method for the large-scale production of α-arbutin.

The design and study on recognition of paracetamol-imprinted polymer for application in quantification of drugs was reported. Base on our previous work, the promising monomer, itaconic acid (IA), was computationally selected rapidly from the virtual library using the interaction energy (ΔE) between a paracetamol (PR) molecule and four monomer molecules as a measure of their interaction. The possible conformation of PR interacting with IA displayed the nature of the interaction between PR and IA; hydrogen bonds (hbs) mainly contribute to this interaction. UV spectra analysis confirmed the occurrence of the hbs interaction between PR and IA at the polymerization stage. The optimal solvents for porogen and eluant were determined by the strength of hbs interaction between PR and the solvents, which were calculated employing density functional theory. The corresponding molecularly imprinted polymers (MIPs) and non-imprinted polymers were prepared and evaluated. The experimental results were consistent with those calculated, which confirmed the validity of the above-related calculation believed to facilitate the selection of monomers and solvents for the synthesis of MIP at molecular level.

In this paper, a simplified model was set up to give an insight into the properties of molecularly imprinted polymer (MIP) at molecular level using MMFF94 force field. Based on our model, the interaction energies (ΔEs) between monomers and template or its analogues were calculated, and the most possible conformations of template or its analogues interacting with monomers in the molar ratio 1/4 were found. The obtained results using the computational and conformational analysis showed that large ΔE meant more activity sites in the cavities in the resultant polymer giving high affinity and good selectivity, leading to a large imprinting factor and when the ΔE differences were small, the imprinting factors were mainly determined by the activity sites. These were well consistent with the experimental results, which confirmed the validity of the model and method proposed that were believed to benefit screening molecularly imprinted systems rapidly in an experiment-free way instead of trial-and-error approach. Considering the affinity and selectivity, 2,6-bisacrylamide pyridine was predicted to be the optimal monomer used to prepare paracetamol MIP for application in quantification of drugs from the ΔE and possible activity sites.

The aim of the present study is to develop an efficient and cost-effective method for α-arbutin production by using whole-cell of Xanthomonas maltophilia BT-112 as a biocatalyst. Hydroquinone (HQ), substrate for the bioconversion as glucosyl acceptor, was immobilized on H107 macroporous resin to reduce its toxic effect on the cells, and the optimal reaction conditions for α-arbutin synthesis were investigated. When 350 g/L H107 resin (254.5 mM HQ) and 20 g/L (4.2 U/g) of cells were shaken in 10 mL Na2HPO4–KH2PO4 buffer (50 mM, pH 6.5) containing 509 mM sucrose at 35 °C with 150 rpm for 48 h, the final yield of α-arbutin reached 65.9 g/L with a conversion yield of 95.2% based on the amount of HQ supplied. The α-arbutin production was 202% higher than that of the control (free HQ) and the cells maintained its full activity for almost six consecutive batch reactions, indicating a potential for reducing production costs. Additionally, the product was one-step isolated and identified as α-arbutin by 13C NMR and 1H NMR analysis. In conclusion, the combination of whole cells and immobilized hydroquinone (IMHQ) is a promising approach for economical and industrial-scale production of α-arbutin.Graphical abstractDownload full-size imageHighlights► The study provided a promising approach for economical production of α-arbutin. ► H107 resin was selected as hydroquinone immobilization medium. ► The yield of α-arbutin reached 65.9 g/L with a conversion yield of 95.2%. ► The reusability of Xanthomonas maltophilia BT-112 cells reached six batches.

The Candida sp. lipase prepared in our lab was used for the resolution of racemic ibuprofen. In order to study the effects of alcohol and solvent on the performance of Candida sp. lipase in enantioselective esterification of racemic ibuprofen, different alcohols were chosen as acyl acceptors in the same solvent, and identical substrates were used in different solvents. The reactions were performed under controlled water activity, thereby permitting the influences of the alcohols and the solvents to be separated from their ability to strip water from the solid enzyme. The results showed that alcohols and solvents had great effects on the performance of Candida sp. lipase.