Didehydrogeranylgeranyl (ΔΔGG): A fluorescent probe for protein prenylation

Article abstract of DOI:10.1021/ja0119144

The first intrinsically fluorescent analog of geranylgeraniol, (2E,6E,8E,10E,12E,14E)-geranylgeraniol (all-trans-ΔΔGGOH·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-ΔΔGGOH 1 showed blue fluorescence in methanol, with λ_ex = 310 nm and λ_em = 410 nm (ε₃₁₀ = 2.4 × 10⁴ M^-1 cm^-1), but was only weakly fluorescent in aqueous solution. The prenyl transferase efficiency for ΔΔGGPP 2 as a substrate for yeast protein geranylgeranyl transferase (PGGTase-I) was 60% relative to that for GGPP. The binding of ΔΔGG-AcCysMe 3 to the recombinant Rho GTPase dissociation inhibitor (RhoGDI) had a K_D of 15.1 ± 1.2 μM, 6-fold lower than the affinity of GG-AcCysMe. Thus, the ΔΔGG moiety is a novel fluorophore suitable for studying the interaction and subcellular localization of prenylated small GTPase proteins in signaling complexes. Copyright