Didehydrofarnesyl diphosphate: an intrinsically fluorescent inhibitor of protein farnesyltransferase

Xiao-Hui Liu; Glenn D Prestwich

doi:10.1016/j.bmcl.2004.02.077

Didehydrofarnesyl diphosphate: an intrinsically fluorescent inhibitor of protein farnesyltransferase

Bioorg Med Chem Lett. 2004 May 3;14(9):2137-40. doi: 10.1016/j.bmcl.2004.02.077.

Authors

Xiao-Hui Liu¹, Glenn D Prestwich

Affiliation

¹ Department of Medicinal Chemistry, The University of Utah, 419 Wakara Way, Suite 205, Salt Lake City, UT 84108-1257, USA.

PMID: 15080995
DOI: 10.1016/j.bmcl.2004.02.077

Abstract

Didehydrofarnesyl diphosphate (delta delta FPP), a fluorescent pentaene analogue of farnesyl diphosphate (FPP), was synthesized using stereoselective Wittig reactions. Although delta delta FPP was not an alternative substrate for yeast protein farnesyltransferase (FTase), the fluorescent analogue was a potent competitive inhibitor with a K(i) value of 8.8 microM (K (m) (FPP) = 27 microM).

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Enzyme Inhibitors / pharmacology*
Fluorescent Dyes / pharmacology*
Polyisoprenyl Phosphates / chemistry
Polyisoprenyl Phosphates / pharmacology*
Sesquiterpenes

Substances

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

Grants and funding

GM 44836/GM/NIGMS NIH HHS/United States