Item – Theses Canada

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OCLC number
46582902
Author
Hum, Gabriel,1973-
Title
The design and synthesis of strained transition state analogues for phosphotriester hydrolysis.
Degree
M. Sc. -- University of Toronto, 1997
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [1999]
Description
2 microfiches.
Notes
Includes bibliographical references.
Abstract
Isomeric 2,5-di-p-nitrophenyl phospholanate esters were synthesized using a modified McCormack reaction. They are to be employed as novel transition state analogues (TSA's) for the hydrolysis of phosphotriesters. Antibodies raised against these haptens are intended to exert strain upon their substrates in order to exercise their catalysis by a combination of ground state destabilization and transition state stabilization. Confirmation of the strained nature of the TSA's was confirmed by determining the C-P-C bond angle by X-ray structure analysis of a 2,5-diphenyl phospholanic acid precursor. The TSA's were conjugated to carrier proteins (bovine serum albumin and keyhole limpet hemocyanin) and used for the generation of monoclonal antibodies. The corresponding bis(p-nitrophenyl)phosphate and p-nitrobenzyl-p-nitrophenyl phosphonate antibody substrates were also synthesized. Preliminary kinetics studies on these substrates showed that they are kinetically stable enough for screening purposes yet sufficiently labile to be susceptible to antibody catalysis.
ISBN
0612292231
9780612292239