title: Ribonuclease A inhibition by carboxymethylsulfonyl-modified xylo- and arabinopyrimidines.
abstract: A group of acidic nucleosides were synthesized to develop a new class of ribonuclease A (RNase A) inhibitors. Our recent study on carboxymethylsulfonyl-modified nucleosides revealed some interesting results in RNase A inhibition. This positive outcome triggered an investigation of the role played by secondary sugar hydroxy groups in inhibiting RNase A activity. Uridines and cytidines modified with SO2 CH2 COOH groups at the 2'- and 3'-positions show good inhibitory properties with low inhibition constant (Ki ) values in the range of 109-17 μM. The present work resulted in a set of inhibitors that undergo more effective interactions with the RNase A active site, as visualized by docking studies.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur (India), Fax: (+91) 3222-255303.
authors.forename: Dhrubajyoti
authors.initials: D
authors.lastname: Datta
authors.forename: Swagata
authors.initials: S
authors.lastname: Dasgupta
authors.forename: Tanmaya
authors.initials: T
authors.lastname: Pathak
mesh_terms: D001088:Arabinonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D019295:Computational Biology; D003562:Cytidine / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors*; D014529:Uridine / Q000737:chemistry
chemical_list: D001088:Arabinonucleotides; D004791:Enzyme Inhibitors; D003562:Cytidine; D012259:Ribonuclease, Pancreatic; D014529:Uridine
keywords: RNase A; carboxymethylsulfonyls; docking; inhibitors; modified nucleosides; pyrimidines