Synthesis of oxazolidinedione derived bicalutamide analogs

The synthesis of chiral oxazolidinedione derived bicalutamide analogs has been discussed.     

A molecular docking model of SARS-CoV S1 protein in complex with its receptor, human ACE2

The exact residues within severe acute respiratory syndrome coronavirus (SARS-CoV) S1 protein and its receptor, human ACE2, involved in their interaction still remain largely undetermined. Identification of exact amino acid residues that are crucial for the interaction of S1 with ACE2 could provide working hypotheses for experimental studies and might be helpful for the development of antiviral inhibitor. In this paper, a molecular docking model of SARS-CoV S1 protein in complex with human ACE2 was constructed. The interacting residue pairs within this complex model and their contact types were also identified. Our model, supported by significant biochemical evidence, suggested receptor-binding residues were concentrated in two segments of S1 protein. In contrast, the interfacial residues in ACE2, though close to each other in tertiary structure, were found to be widely scattered in the primary sequence. In particular, the S1 residue ARG453 and ACE2 residue LYS341 might be the key residues in the complex formation.     

Cavity search: An algorithm for the isolation and display of cavity-like binding regions

Summary A set of algorithms designed to enhance the display of protein binding cavities is presented. These algorithms, collectively entitled CAVITY SEARCH, allow the user to isolate and fully define the extent of a particular cavity. Solid modeling techniques are employed to produce a detailed cast of the active site region, which can then be color-coded to show electrostatic and steric interactions between the protein cavity and a bound ligand.     

OVID and SUPER: Two overlap programs for drug design

Summary Two programs, OVID and SUPER, for exploring the similarity of molecules with respect to their action at a receptor are described. OVID accepts two molecules as input and optimizes the three-dimensional overlap of specified atoms in one molecule with specified atoms in the second molecule. The result is expressed as a percent of the theoretical maximum. OVID gives a quantitative measure of the extent of a guessed correspondence between two molecules based on volume overlap of selected atoms. The Achilles' heel of OVID is that the correspondence between the two molecules has to be guessed. We realized that it would be better to systematically examine all possible correspondences of two structures to minimize the chance of overlooking a superior correspondence. We created SUPER to satisfy this need. SUPER accepts two molecules as input and finds the top twenty correspondences of their surfaces and charge distributions, giving a quantitative measure of the extent of each correspondence. An instructive example of the application of OVID and SUPER to the design of leukotriene D₄ receptor antagonists is described. SUPER appears to be a practical brainstorming tool for the medicinal chemist trying to understand how molecules whose structures may not resemble one another in an obvious way can bind to the same site.     

Genomic variation and point mutations analysis of Indian COVID-19 patient samples submitted in GISAID database

Corona virus disease 2019 (COVID-19) endemic has havoc on the world; the causative virus of the pandemic is SARS CoV-2. Pharmaceutical companies and academic institutes are in continuous efforts to identify anti-viral therapy or vaccines, but the most significant challenge faced is the highly evolving genome of SARS CoV-2, which is imparting evolutionary selective benefits to the virus. To understand the viral mutations, we have retrieved nine hundred and thirty-four samples from different states of India via the GISAID database and analyzed the frequency of all types of point mutation in all structural, non-structural proteins, and accessory factors of SARS CoV-2. Spike glycol protein, nsp3, nsp6, nsp12, N and NS3 were the most evolving proteins. High frequency point mutations were Q496P (nsp2), A380V (nsp4), A994D (nsp3), L37F (nsp6), P323L & A97V (nsp12), Q57H (ns3), D614G (S), P13L (N), R203K (N), G204R (N) and S194L (N).     

受体生物传感器的研究进展

综述了利用各种生物材料中的膜受体蛋白作为分子识别元件的受体生物传感器研究的最新进展。主要从离体受体传感器、细胞受体传感器和神经组织受体传感器3个方面，讨论了它们的特点和存在的问题，并展望了受体生物传感器未来的发展方向。共引用文献42篇。     

Practical ex-chiral-pool methodology for the synthesis of dopaminergic tetrahydroindoles

Chemo- and regioselective transformations of asparagine gave access to optically active 5- and 6-amino tetrahydroindolizines when the 3-aminobutyrolactone (S)-2 was employed as a key intermediate. The target compounds were approached by a sequential and regiocontrolled bis-electrophilic attack in the positions 2 and 3 of the pyrrole ring system. Receptor binding experiments showed stereocontrolled receptor recognition leading to the D3 selective agonist (S)-8 with D3 binding that is comparable to the natural neurotransmitter dopamine.     

Partial-filling affinity capillary electrophoresis

Partial-filling affinity capillary electrophoresis (PFACE) is used to examine the binding interactions between two model biological systems: D-Ala-D-Ala terminus peptides to the glycopeptide antibiotic vancomycin (Van) from Streptomyces orientalis, and arylsulfonamides to carbonic anhydrase B (CAB, EC 4.2.1.1, bovine erythrocytes). Using these two systems, modifications in the PFACE technique are demonstrated including flow-through PFACE (FTPFACE), competitive flow-through PFACE (CFTPFACE), on-column ligand synthesis PFACE (OCLSPFACE), and multiple-step ligand injection PFACE (MSLIPFACE). In PFACE small plugs of sample are injected into the capillary column and an equilibrium is established between receptor and ligand during electrophoresis. Binding constants are then obtained by Scatchard analysis using changes in the migration time of the receptor/ligand on changing the concentration of the ligand/receptor. Data demonstrating the quantitative potential of these methods are presented. This review focuses on the unique capabilities of the different PFACE techniques as applied to two model biological systems.