Ribonuclease A (RNase A) works at the junction of the transcription and translation processes, and thereby maintains the cellular RNA levels. RNase A is a member of a superfamily of enzymes that exhibits angiogenic, neurotoxic, antitumor, or immunosuppressive activities. Structural homology among the various members of this family permits the use of Ribonuclease A (RNase A) as a model system to explore the structure-activity relationship.<br/>1,2,3-Triazoles, having high chemical stability and hydrogen bonding ability are effective linkers in the synthesis of densely functionalized hybrid molecules. We have been designing RNase A inhibitors functionalized with carboxylic acid groups capable of binding with the positively charged active site of RNase A.<br/>In the present work a new series of thymidine-derived triazolylated carboxylic acid compounds have been synthesized and their inhibitory properties were studied. Inhibition of the enzyme was qualitatively confirmed using Agarose gel based assay and the inhibition constant values were obtained from enzyme kinetics indicating that the efficiency of inhibition increases with the number of carboxylic acid groups. Additionally, docking studies indicated strong electrostatic interaction between the carboxylic acid groups of the inhibitors with the amino acid residues present at the active site of RNase A.

Inhibition of ribonucleolytic activity of RNase A by triazolylated thymidines

2019 Spring National Meeting

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