Inhibition of ribonuclease A by nucleoside-dibasic acid conjugates.
We report the inhibition of the ribonucleolytic activity of ribonuclease A (RNase A) by nucleoside-dibasic acid conjugates for the first time. Agarose gel and precipitation assays show that the spacer length and the pK(a) of the carboxylic group have an important role in the inhibitory capacity. Kinetic experiments indicate a competitive mode of inhibition with inhibition constant (K(i)) value of 132+/-3 microM for Oxa-aT. Docking studies revealed that the carboxylic group of the most active compounds is within hydrogen bonding distance of His-12, Lys-41 and His-119.
Debnath
Joy
J
Department of Chemistry, Indian Institute of Technology, Kharagpur, Kharagpur 721 302, India.
Dasgupta
Swagata
S
Pathak
Tanmaya
T
D000143:Acids / Q000737:chemistry; D000818:Animals; D002417:Cattle; D008958:Models, Molecular; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
D000143:Acids; D009705:Nucleosides; D012259:Ribonuclease, Pancreatic