Inhibition of ribonuclease A by nucleoside-dibasic acid conjugates
Joy Debnath1, Swagata Dasgupta, Tanmaya Pathak
1Department of Chemistry, Indian Institute of Technology, Kharagpur, Kharagpur 721 302, India.
Abstract:
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.
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