The alpha-chymotrypsin-catalysed hydrolyses of derivatives of n-acetyl-L-phenylalanine methyl ester and of methyl hippurate
Abstract (Summary)N-Acetyl-L-phenylalanine methyl ester and 23 of its derivatives (all substituted at the phenyl ring of the parent compound) have been evaluated as substrates of [alpha]-chymotrypsin. The results are interpreted in terms of a model of the active site of the enzyme. An elaboration of the model for the locus of the active site where the side chains of the amino acid derivatives are bound is offered. The rates of the [alpha]-chymotrypsin-catalyzed hydrolyses of N-acetyl-N-methyl-L-tyrosine methyl ester and of methyl parahydroxyhydrocinnamate were evaluated. Comparisons among the kinetic constants for these reactions and for the [alpha]-chymotrypsin-catalyzed hydrolyses of N-acetyl-L-tyrosine methyl ester are made. The effect of the structural modifications of the acetylamino group of N-acetyl-L-tyrosine methyl ester on the kinetic constants of its [alpha]-chymotrypsin-catalyzed reaction are again interpreted in terms of a model of the active site of [alpha]-chymotrypsin. Finally, four derivatives of methyl hippurate were evaluated as substrates of [alpha]-chymotrypsin. Two other derivatives of methyl hippurate were reversible competitive inhibitors of [alpha]-chymotrypsin. All six were substituted on the benzene ring of the benzoylamino group. The results are compatible with the proposal that the benzamido groups of methyl hippurate derivatives interact with the same locus of the enzymatic active site as do the side chains of derivatives of N-acetyl-L-phenylalanine methyl ester.
School Location:USA - California
Source Type:Master's Thesis
Date of Publication:12/10/1964