Ribonuclease A inhibition by carboxymethylsulfonyl-modified xylo- and arabinopyrimidines

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.