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Cyclohexane diester analogues of phorbol ester as potential activators of protein kinase C.

Authors
  • Kerr, D E
  • Kissinger, L F
  • Shoyab, M
Type
Published Article
Journal
Journal of medicinal chemistry
Publication Date
Jul 01, 1990
Volume
33
Issue
7
Pages
1958–1962
Identifiers
PMID: 2362276
Source
Medline
License
Unknown

Abstract

Phospholipid-dependent, Ca2(+)-sensitive protein kinase (protein kinase C) is activated by the plant product phorbol ester at nanomolar concentrations and also in vivo at micromolar concentrations by diacylglycerols. We designed and synthesized cyclohexane diester analogues of the phorbol ester C ring as potential high-affinity activators of protein kinase C. We proposed that the necessary pharmacophore of phorbol ester could be mimicked by diesters of appropriately substituted cyclohexanediols. A series of 1,2-cyclohexanediol diesters with different substituents at position 4 was synthesized. These substituents were designed to mimic the 6,7-double bond and C-20 hydroxy of phorbol ester. Competitive binding vs [3H]phorbol dibutyrate determined that these compounds have an affinity for protein kinase C of 1 mM or more, and thus they do not bind to nor are they activators of this enzyme.

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