Stereochemistry matters: Inhibition of carbonic anhydrase II by amino acid derived sulfamates depends on their absolute configuration

Abstract

Aminoalcohols were converted into the corresponding enantiomeric phenylsulfonamide sulfamates. These compounds proved to be inhibitors of carbonic anhydrase II. Interestingly, a sulfamate derived from (S)-tryptophan was no inhibitor at all while its (R) configurated enantiomer was an excellent inhibitor of carbonic anhydrase II (CA II). A rationale can be deduced from molecular modeling studies. The sulfamates derived from (R) or (S) proline held very low inhibition constants for this enzyme as Ki = 0.77 μM and 0.70 μM, respectively.