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I. Thiocarbamate studies. II. Preliminary investigations of the alpha-chymotrypsin catalyzed hydrolysis of acylated amino acid esters. III. The alpha-chymotrypsin catalyzed hydrolysis of methyl hippurate and of benzoyl-L-valine methyl ester. IV. The enzyme inhibitor dissociation constants of some N-acetyl amino acid N'-methylamides

Citation

Applewhite, Thomas Hood (1956) I. Thiocarbamate studies. II. Preliminary investigations of the alpha-chymotrypsin catalyzed hydrolysis of acylated amino acid esters. III. The alpha-chymotrypsin catalyzed hydrolysis of methyl hippurate and of benzoyl-L-valine methyl ester. IV. The enzyme inhibitor dissociation constants of some N-acetyl amino acid N'-methylamides. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/03FF-7N17. https://resolver.caltech.edu/CaltechETD:etd-07082004-132616

Abstract

The known reactions of N,S-diphenylthiocarbamate were extended by studies of the effects of various reagents and conditions. The results are discussed in terms of previously suggested reaction mechanisms.

The mixed anhydrides between S-phenylthiocarbonylchloride and carboxylic acids were briefly investigated as preparative intermediates. Low yields of the expected products offset the utility of this method.

The non-reactivity of secondary amine S-phenylthiocarbamates was further demonstrated with N-pentamethylene-S-phenylthiocarbamate. The inert nature of this compound indicates that the effects are not due to steric hindrance.

A brief investigation of the reactions of S-benzylthio- and 0-benzyl-N-phenylcarbamate suggest that they have little value as preparative intermediates as compared to the S- and 0-phenyl derivatives.

Some S-phenylthiocarbamates of amino acid derivatives were prepared, and their use in a polymerization reaction and stepwise dipeptide synthesis is described. The results suggest that the various methods are not as elegant as indicated earlier.

A recently developed automatic titration instrument was employed in a preliminary study of the [alpha]-chymotrypsin catalyzed hydrolysis of some acylated amino acid esters. A useable system was developed, and some preliminary results were obtained concerning techniques, data treatment, surface effects and steric effects in enzyme catalyzed reactions.

The kinetics of the [alpha]-chymotrypsin catalyzed hydrolysis of methyl hippurate were re-investigated. In addition, the enzyme-inhibitor dissociation constants of two competitive inhibitors were re-determined. The results are compared with values obtained earlier.

Benzoyl-L-valine methyl ester, a new substrate for this enzyme, was studied in the catalyzed reaction employing the above techniques. Additional refinements in technique and errors in this system are discussed.

A number of potential competitive inhibitors, the N-acetyl amino acid N'-methylamides, were synthesized and tested for inhibitory activity in the [alpha]-chymotrypsin catalyzed hydrolysis of methyl hippurate and benzoyl-L-valine methyl ester. The results indicate that, of the compounds studied, only those containing an aromatic residue have a measurable effect in the present systems.

Item Type:Thesis (Dissertation (Ph.D.))
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 1956
Record Number:CaltechETD:etd-07082004-132616
Persistent URL:https://resolver.caltech.edu/CaltechETD:etd-07082004-132616
DOI:10.7907/03FF-7N17
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2824
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:13 Jul 2004
Last Modified:21 Dec 2019 02:01

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