Exploration of GGTase-I substrate requirements. Part 1: Synthesis and biochemical evaluation of novel aryl-modified geranylgeranyl diphosphate analogs

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3499-502. doi: 10.1016/j.bmcl.2016.06.034. Epub 2016 Jun 16.


Protein geranylgeranylation is a type of post-translational modification that aids in the localization of proteins to the plasma member where they elicit cellular signals. To better understand the isoprenoid requirements of GGTase-I, a series of aryl-modified geranylgeranyl diphosphate analogs were synthesized and screened against mammalian GGTase-I. Of our seven-member library of compounds, six analogs proved to be substrates of GGTase-I, with 6d having a krel=1.93 when compared to GGPP (krel=1.0).

Keywords: Aryl-modified GGPP analogs; GGTase-I; Geranylgeranylation; Post-translational modification; Protein prenylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Polyisoprenyl Phosphates / chemical synthesis
  • Polyisoprenyl Phosphates / chemistry
  • Polyisoprenyl Phosphates / pharmacology*
  • Structure-Activity Relationship


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