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Rationally designed inhibitors of inosine monophosphate dehydrogenase.

Authors
  • Zhang, H Z
  • Rao, K
  • Carr, S F
  • Papp, E
  • Straub, K
  • Wu, J C
  • Fried, J
Type
Published Article
Journal
Journal of medicinal chemistry
Publication Date
Jan 03, 1997
Volume
40
Issue
1
Pages
4–8
Identifiers
PMID: 9016322
Source
Medline
License
Unknown

Abstract

Functionalized 2-alkyl derivatives of inosinic acid have been synthesized to serve as reversible as well as irreversible inhibitors of the human type II enzyme inosine monophosphate dehydrogenase. These compounds were designed to react with Cys-331 of the enzyme to form covalent bonds so as to interfere with the normal enzyme mechanism which involves attack of Cys-331 at C-2 of the substrate. Mass spectrometric analysis of the reaction products after enzymatic degradation confirmed the appropriateness of the inhibitor design.

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