Aromatic farnesyl diphosphate analogues: vinyl triflate-mediated synthesis and preliminary enzymatic evaluation.
A stereocontrolled vinyl triflate-based synthetic route has been used to prepare four analogues of farnesyl diphosphate (FPP) where the terminal isoprene units have been replaced with aromatic moieties. Two of these analogues exhibit no productive interaction with protein farnesyltransferase, but the 2-naphthyl derivative 2 is a modest inhibitor of the enzyme, and the para-biphenyl derivative 4 is a surprisingly effective alternative substrate.
Zhou
Chunmei
C
Department of Pharmaceutical Sciences, College of Pharmacy and AHP, Wayne State University, Detroit, MI 48202, USA.
Shao
Ying
Y
Gibbs
Richard A
RA
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D012717:Sesquiterpenes; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase