title: Photoactive analogs of farnesyl diphosphate and related isoprenoids: design and applications in studies of medicinally important isoprenoid-utilizing enzymes.
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.
authors: Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Jeffrey S
authors: JS
authors: Vervacke
authors: Yen-Chih
authors: YC
authors: Wang
authors: Mark D
authors: MD
authors: Distefano
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019755:Carbon-Carbon Lyases / Q000737:chemistry / Q000378:metabolism; D055808:Drug Discovery; D051231:Farnesyltranstransferase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D019920:Photoaffinity Labels / Q000737:chemistry* / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000737:chemistry* / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001577:Benzophenones; D019920:Photoaffinity Labels; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; D013729:Terpenes; C004808:farnesyl pyrophosphate; D051231:Farnesyltranstransferase; D019755:Carbon-Carbon Lyases; C051130:trichodiene synthetase