University of Illinois Urbana-Champaign

Synthesis and evaluation of aziridine and symmetry-based epoxide affinity labels for HIV-1 protease

Kreps, James Jonathan

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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
Issue Date
1996
Doctoral Committee Chair(s)
Katzenellenbogen, John A.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
  • Chemistry, Organic
  • Chemistry, Pharmaceutical
Language
eng
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.
Type of Resource
text
Permalink
http://hdl.handle.net/2142/20034
Copyright and License Information
Copyright 1996 Kreps, James Jonathan

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