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
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|
|Thesis Availability:||Public (worldwide access)|
|Defense Date:||1 January 1961|
|Author Email:||abrash8 (AT) aol.com|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Imported from ETD-db|
|Deposited On:||20 Mar 2006|
|Last Modified:||10 Feb 2014 23:13|
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