CONFORMATIONAL STUDIES ON PEPTIDES AS ENZYME-INHIBITORS - CHYMOTRYPSIN INHIBITORS USING BOWMAN-BIRK TYPE AS MODELS

A complete structural characterization in solution, by NMR spectroscop y, and in vacuo, by molecular dynamic simulations, of two synthetic pe ptide fragments from SBBI (Soybean Bowman-Birk Inhibitor) is reported. Peptide 197, corresponding to the SBBI(41-49) chymotrypsin recognitio n site, has free N- and C-terminal groups, while peptide 212, correspo nding to the Leu 16-SBBI(14-22) has uncharged and fully protected term inal ends. Peptide 212 shows significant antichymotryptic activity whi le peptide 197 is inactive. Neither of the two peptides shows anti-try ptic activity. The structural information obtained in the present pape r suggests a quantitative structure-activity relationship which may he lp both in understanding the mechanism of action of protease inhibitor s, and in providing new directions for the rational design of more spe cific and potent inhibitors.