Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1889-92. doi: 10.1016/j.bmcl.2008.02.014. Epub 2008 Feb 12.

Abstract

Protein prenyl transferases have been a focus of anti-cancer drug discovery in recent years due to their roles in post-translational modification of small GTP binding proteins. Attention is now turning to the development of GGTase I inhibitors. Here, we present the synthesis and biological evaluation of four GGPP analogs versus mammalian GGTase I and the discovery that 7-allyl GGPP is a surprisingly efficient GGTase I substrate.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Structure
  • Polyisoprenyl Phosphates / chemical synthesis*
  • Polyisoprenyl Phosphates / pharmacology*
  • Protein Prenylation
  • Protein Processing, Post-Translational

Substances

  • Polyisoprenyl Phosphates
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Farnesyltranstransferase
  • geranylgeranyl pyrophosphate