Farnesyl diphosphate analogues with omega-bioorthogonal azide and alkyne functional groups for protein farnesyl transferase-catalyzed ligation reactions.
Eleven farnesyl diphosphate analogues, which contained omega-azide or alkyne substituents suitable for bioorthogonal Staudinger and Huisgen [3 + 2] cycloaddition coupling reactions, were synthesized. The analogues were evaluated as substrates for the alkylation of peptide cosubstrates by yeast protein farnesyl transferase. Five of the diphosphates were good alternative substrates for farnesyl diphosphate (FPP). Steady-state kinetic constants were measured for the active compounds, and the products were characterized by HPLC and LC-MS. Two of the analogues gave steady-state kinetic parameters (kcat and Km) very similar to those of the natural substrate.
Labadie
Guillermo R
GR
Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Viswanathan
Rajesh
R
Poulter
C Dale
CD
D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D007700:Kinetics; D013058:Mass Spectrometry; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis*; D012717:Sesquiterpenes / Q000138:chemical synthesis*
D000480:Alkynes; D001386:Azides; D010455:Peptides; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase