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

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 (K-i) 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 P-1 site of ribonuclease A. Typical harsh conditions used for SO3H incorporation were replaced with milder reaction conditions. The uridine analogue showing a K-i value of 0.96 mu M 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.