Analogues of geranyl pyrophosphate as inhibitors of prenyltransferase.
Six analogues of geranyl pyrophosphate (the monophosphates of geraniol and tetrahydrogeraniol, and the pyrophosphates of nerol, octan-1-ol, tetrahydrogeraniol and citronellol) were synthesized, and were found to be inhibitors of pig liver prenyl- (geranyl-)transferase. The effects of each analogue were analysed in kinetic experiments, which showed the pyrophosphates of citronellol, tetrahydrogeraniol and octan-1-ol to be the most potent inhibitors. The results are interpreted to support a previous hypothesis that the main forces in the binding of substrates to prenyltransferase are non-specific lipophilic forces and a pyrophosphate-binding force.
D000438:Alcohols; D000818:Animals; D007700:Kinetics; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D010756:Phosphoric Acids / Q000378:metabolism*; D013552:Swine; D013729:Terpenes / Q000378:metabolism*; D014166:Transferases / Q000037:antagonists & inhibitors*
D000438:Alcohols; D010756:Phosphoric Acids; D013729:Terpenes; D014166:Transferases