title: 5'-Modified pyrimidine nucleosides as inhibitors of ribonuclease A.
abstract: Four 5'-deoxy-5'-nipecotic acid substituted pyrimidine nucleosides were synthesized and characterized. Their inhibitory activities towards ribonuclease A (RNase A) have been studied by enzyme kinetics and docking experiments. All inhibition constants obtained were in the sub-millimolar range. Biochemical analysis shows that the uridine derivative is more potent than the corresponding thymidine derivatives and that the inhibition is competitive in nature. For thymidine derivatives, the 3'-hydroxy group plays an important role in binding as well as in inhibition. Docking studies also support the experimental results. In the docking conformation the uridine derivative was found to bind to the P(1)P(2) subsite with the acid group within hydrogen bonding distance of the active site histidine residues.
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Samanta
authors.forename: Swagata
authors.initials: S
authors.lastname: Dasgupta
authors.forename: Tanmaya
authors.initials: T
authors.lastname: Pathak
mesh_terms: D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011487:Protein Conformation; D011741:Pyrimidine Nucleosides / Q000737:chemistry / Q000494:pharmacology*; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011741:Pyrimidine Nucleosides; D012259:Ribonuclease, Pancreatic