QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS IN THE SYNTHESIS OF ACXYNH2 DIPEPTIDES BY ALPHA-CHYMOTRYPSIN IN REVERSED MICELLES

Modified dipeptides of the type AcXYNH2 were synthesized by alpha-chym otrypsin in reversed micelles of tetradecyltrimethylammonium bromide i n heptane/octanol using substrates AcXOEt (X = Phe, Tyr, Trp) as acyl donors and YNH2 (Y = Gly, Ala, Ser, Val, Leu, Ile, Phe) as acyl accept ors. With the exception of TyrPhe, all syntheses were accomplished wit h yields ranging from 24-96% in less than 1 h. The dipeptides PheLeu, PheIle, PheVal, TyrIle, and TyrVal precipitated in the media during re action. The transport of the ester substrates from the organic bulk to the water pool of the micelles was identified as the rate-limiting st ep. The amide nucleophilicity was found to decrease with an increase i n hydrophobicity: Ser > Ala > Gly > Val > Ile > Leu. A correlation bet ween the dipeptide yields and their hydrophobicity, accessible surface area, and molecular weight showed that smaller and more hydrophilic d ipeptides were synthesized with higher yields. (C) 1997 Elsevier Scien ce Inc.