Synthesis of geranyl S-thiolodiphosphate. A new alternative substrate/inhibitor for prenyltransferases.
The tris(tetra-n-butylammonium) salt of thiopyrophosphate 5 was prepared from trimethyl phosphate in four steps. Treatment of geranyl bromide with 5 gave an 80% yield of geranyl S-thiolodiphosphate (6). Thiolodiphosphate 6 is substantially less reactive than geranyl diphosphate (7) in the prenyl transfer reaction catalyzed by farnesyl diphosphate synthase and is a good inhibitor of the enzyme.
Phan
R M
RM
Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Poulter
C D
CD
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004122:Dimethylallyltranstransferase / Q000037:antagonists & inhibitors*; D011756:Diphosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051228:Geranyltranstransferase; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D011756:Diphosphates; D004791:Enzyme Inhibitors; D009946:Organothiophosphorus Compounds; C046010:monothiopyrophosphoric acid; D019883:Alkyl and Aryl Transferases; D004122:Dimethylallyltranstransferase; D051228:Geranyltranstransferase