Synthesis of high specific activity 35S‐labelled N‐methanesulfonyl farnesylcysteine and a photoactive analog

摘要: Prenylated cysteine analogs, which mimic the prenylated residue of GTP-binding proteins (G-proteins), have been used in a variety contexts for study G-protein behavior. In earlier work this area, we prepared photoactive analog [35S]4 and showed that it labelled RhoGDI upon photolysis; those results were consistent with idea GDI contains an isoprenoid binding site. Here, describe preparation [35S]N-methanesulfonyl analogs (1a 2a) N-acetyl farnesylcysteine its methyl ester together improved synthetic procedure 3 4; specific activities ∼1100 Ci/mmol achieved. Compounds 1a 2a unlabelled form as competitors photolysis reactions to show methanesulfonamido group is reasonable acetamide substitution. Additional experiments [35S]3 can cross-link both purified crude bacterial extract. However, extent cross-linking obtained ([35S]3) significantly less than observed free acid ([35S]4) despite fact esterified probably more closely reflects structure C-terminus protein; using GDI·Cdc42 co-crystal structure, structural basis these discussed. Copyright © 2002 John Wiley & Sons, Ltd.