Sulfonic nucleic acids (SNAs): a new class of substrate mimics for ribonuclease A inhibition

Abstract

Sulfonic nucleic acids were identified as inhibitors of ribonuclease A (RNase A). The incorporation of a strongly acidic group (sulfonic, –SO3H) at the 3′-end of pyrimidine nucleosides thymidine and uridine was prompted by the low inhibition constant (Ki) values recorded for carboxymethylsulfonyl (–SO2CH2CO2H) and –CO2H functionalized nucleosides. It was envisaged that the sulfonic acid-modified pyrimidines would bind effectively with the positively charged P1 site of ribonuclease A. Typical harsh conditions used for SO3H incorporation were replaced with milder reaction conditions. The uridine analogue showing a Ki value of 0.96 μM elicited a better result than the thymidine-modified inhibitor. Notably, it was also the best result among all modified non-phosphate acidic nucleosides reported and screened so far as RNase A inhibitors.