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 SO 2 CH 2 COOH groups at the 2′‐ and 3′‐positions show good inhibitory properties with low inhibition constant ( K i ) values in the range of 109–17 μ M . 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.