title: Didehydrogeranylgeranyl (Delta Delta GG): a fluorescent probe for protein prenylation.
abstract: The first intrinsically fluorescent analog of geranylgeraniol, (2E,6E,8E,10E,12E,14E)-geranylgeraniol (all-trans-DeltaDeltaGGOH.1) has been synthesized stereoselectively and shown to substitute for the geranylgeranyl (GG) moiety in prenyl transferase reactions and in protein-ligand binding assays. All-trans-DeltaDeltaGGOH 1 showed blue fluorescence in methanol, with lambdaex = 310 nm and lambdaem = 410 nm (epsilon310 = 2.4 x 104 M-1 cm-1), but was only weakly fluorescent in aqueous solution. The prenyl transferase efficiency for DeltaDeltaGGPP 2 as a substrate for yeast protein geranylgeranyl transferase (PGGTase-I) was 60% relative to that for GGPP. The binding of DeltaDeltaGG-AcCysMe 3 to the recombinant Rho GTPase dissociation inhibitor (RhoGDI) had a KD of 15.1 +/- 1.2 muM, 6-fold lower than the affinity of GG-AcCysMe. Thus, the DeltaDeltaGG moiety is a novel fluorophore suitable for studying the interaction and subcellular localization of prenylated small GTPase proteins in signaling complexes.
authors.affiliation: Department of Medicinal Chemistry and the Center for Cell Signaling, 30 South 2000 East, Room 201, The University of Utah, Salt Lake City, Utah 84112-5820, USA.
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Liu
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry / Q000378:metabolism; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry / Q000378:metabolism; D017368:Protein Prenylation; D013237:Stereoisomerism; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: D004224:Diterpenes; D005456:Fluorescent Dyes; D020730:Guanine Nucleotide Dissociation Inhibitors; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; C017338:geranylgeraniol; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I