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Description
Title: | Synthesis and evaluation of aziridine and symmetry-based epoxide affinity labels for HIV-1 protease |
Author(s): | Kreps, James Jonathan |
Doctoral Committee Chair(s): | Katzenellenbogen, John A. |
Department / Program: | Chemistry |
Discipline: | Chemistry |
Degree Granting Institution: | University of Illinois at Urbana-Champaign |
Degree: | Ph.D. |
Genre: | Dissertation |
Subject(s): | Chemistry, Organic
Chemistry, Pharmaceutical |
Abstract: | Affinity labels have been prepared for HIV-1 protease. The synthesis of three symmetry-based epoxides and an aziridine analog of 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) are reported. Assay procedures were developed to allow testing for both reversible and irreversible inhibition of HIV-1 protease, based on an internally-quenched fluorogenic substrate. Of eleven compounds assayed for reversible inhibition, five demonstrated modest to potent activities (K$\rm\sb{i}$'s ranging from 70 $\mu$M to 10 nM). Five compounds were tested for irreversible inhibition of the protease; of these, EPNP and three others were observed to inhibit the enzyme in a time-dependent manner consistent with irreversible inhibition. The aziridine analog of EPNP was found to be approximately fifteen times less potent than EPNP; two C$\sb2$ symmetric epoxides exhibited modes time-dependent inhibition of HIV-1 protease. |
Issue Date: | 1996 |
Type: | Text |
Language: | English |
URI: | http://hdl.handle.net/2142/20034 |
ISBN: | 9780591198690 |
Rights Information: | Copyright 1996 Kreps, James Jonathan |
Date Available in IDEALS: | 2011-05-07 |
Identifier in Online Catalog: | AAI9712337 |
OCLC Identifier: | (UMI)AAI9712337 |
This item appears in the following Collection(s)
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Graduate Dissertations and Theses at Illinois
Graduate Theses and Dissertations at Illinois -
Dissertations and Theses - Chemistry