STRUCTURE ACTIVITY RELATIONSHIP IN THE HYDROLYSIS OF N-BENZOYLPHENYLALANINE ESTERS CATALYZED BY ALPHA-CHYMOTRYPSIN

The alteration by DMF of the active site of native alpha-chymotrypsin was analyzed by QSAR and molecular mechanics methodologies. The hydrolysis of several synthetic esters was used as the reaction model. In order to analyze the structural parameters of the substrates that influence enzymatic activity, classic monovalent isosters of phenylalanine were synthesized to be used as model substrates (ortho, meta and para F, Cl, Me; m-Br and p-OH). The conformation of the ester that interacts with the enzyme has been determined. The dimensions of the 'ar' active subsite of alpha-chymotrypsin have been revised according to the results. The main variables that influence the stearase activity of alpha-chymotrypsin - expressed as log(1/k) - and the binding constant - log(1/K(m)) - have been analyzed. The active conformation of the ester (used in the binding process) was determined by QSAR analysis.