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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
Degree Granting Institution:University of Illinois at Urbana-Champaign
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
Rights Information:Copyright 1996 Kreps, James Jonathan
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9712337
OCLC Identifier:(UMI)AAI9712337

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