I. Steric and electrostatic repulsions in the inhibition of alpha-chymotrypsin catalysed hydrolyses by indole derivatives II. Steric requirements for substrates of alpha-chymotrypsin

Citation

Abrash, Henry Ivan (1961) I. Steric and electrostatic repulsions in the inhibition of alpha-chymotrypsin catalysed hydrolyses by indole derivatives II. Steric requirements for substrates of alpha-chymotrypsin. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-03202006-085153

Abstract

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The enzyme-inhibitor dissociation constants, i.e., [...], were evaluated for the six isomeric pairs of C-substituted indolecarboxylate ions and carboxamides. The variation of [...] with the position and nature of the substituent indicates that the enzyme-indole complex exhibits a high degree of steric hindrance near the 4 position of the indole ring and electrostatic repulsion due to a negative group near the indole nitrogen.

The synthesis of D,L-beta,beta-dimethylphenylalanine was modified by use of air oxidation of 4, 6-di-(alpha,alpha-dimethylbenzyl)pyrogallol to 3,5-di-(alpha,alpha-dimethylbenzyl)coumalic acid and permanganate oxidation of this product to obtain alpha-keto-beta-phenylisovaleric acid. The by-products of the air oxidation were investigated.

D,L-2,6-Dimethyltyrosine, a previously unreported amino acid, and several of its derivatives were synthesized.

Studies on the rates of alpha-chymotrypsin catalysed hydrolyses of N-acetyl-D,L-t-leucine methyl ester, N-acetyl-D,L-beta,beta-dimethyl-phenylalanine methyl ester and N-acetyl-D,L-2,6-dimethyltyrosine methyl ester indicate the presence of a strong beta steric effect.

Methods of resolution of D,L-beta,beta-dimethylphenylalanine and D,L-2,6-dimethyltyrosine derivatives were investigated.

Methyl indole-2-carboxylate is not a substrate of alpha-chymotrypsin.

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