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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

The enzyme-inhibitor dissociation constants, i.e., KI's, were evaluated for the six isomeric pairs of C-substituted indolecarboxylate ions and carboxamides. The variation of KI 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-β,β-dimethylphenylalanine was modified by use of air oxidation of 4, 6-di-(α,α-dimethylbenzyl)pyrogallol to 3,5-di-(α,α-dimethylbenzyl)coumalic acid and permanganate oxidation of this product to obtain alpha-keto-β-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 α-chymotrypsin catalysed hydrolyses of N-acetyl-D,L-t-leucine methyl ester, N-acetyl-D,L-β,β-dimethyl-phenylalanine methyl ester and N-acetyl-D,L-2,6-dimethyltyrosine methyl ester indicate the presence of a strong β steric effect.

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

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

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:chymotrypsin; indole
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Niemann, Carl G.
Thesis Committee:
  • Unknown, Unknown
Defense Date:1 January 1961
Author Email:abrash8 (AT) aol.com
Record Number:CaltechETD:etd-03202006-085153
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-03202006-085153
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1032
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:20 Mar 2006
Last Modified:10 Feb 2014 23:13

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