Photoactive Analogs of Farnesyl Diphosphate and Related Isoprenoids: Design and Applications in Studies of Medicinally Important Isoprenoid- Utilizing Enzymes

Jeffrey      S. Vervacke; Yen-Chih      Wang; Mark      D. Distefano

doi:10.2174/0929867311320120008

Abstract

Farnesyl diphosphate (FPP) is an important metabolic intermediate in the biosynthesis of a variety of molecules including sesquiterpenes and the side chains of a number of cofactors. FPP is also the source of isoprenoid side chains found attached to proteins. Enzymes that employ FPP as a substrate are of interest because they are involved in the semisynthesis of drugs as well as targets for drug design. Photoactive analogs of FPP have been useful for identifying enzymes that use this molecule as a substrate. A variety of photocrosslinking groups have been employed to prepare FPP analogs for use in such experiments including aryl azides, diazotrifluoropropionates and benzophenones. In this review, the design of these probes is described along with an examination of how they have been used in crosslinking experiments.

Keywords: Aryl azide, benzophenone, diazoester, farnesyl diphosphate, farnesyl diphosphate synthase, geranylgeranyl diphosphate, photoaffinity labeling, photocrosslinking, protein farnesyltransferase, sesquiterpene cyclase