Aromatic farnesyl diphosphate analogues: vinyl triflate-mediated synthesis and preliminary enzymatic evaluation

Bioorg Med Chem Lett. 2002 May 20;12(10):1417-20. doi: 10.1016/s0960-894x(02)00187-7.

Abstract

A stereocontrolled vinyl triflate-based synthetic route has been used to prepare four analogues of farnesyl diphosphate (FPP) where the terminal isoprene units have been replaced with aromatic moieties. Two of these analogues exhibit no productive interaction with protein farnesyltransferase, but the 2-naphthyl derivative 2 is a modest inhibitor of the enzyme, and the para-biphenyl derivative 4 is a surprisingly effective alternative substrate.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / chemistry
  • Binding Sites
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Kinetics
  • Models, Molecular
  • Molecular Conformation
  • Polyisoprenyl Phosphates / chemical synthesis*
  • Polyisoprenyl Phosphates / chemistry
  • Polyisoprenyl Phosphates / pharmacology
  • Protein Conformation
  • Sesquiterpenes
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Polyisoprenyl Phosphates
  • Sesquiterpenes
  • farnesyl pyrophosphate
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase