Photocaged Cysteine Peptides for Studying Protein Farnesylation

摘要

Mutant Ras proteins are responsible for 30% of human cancers, and famesylation is a key step that activates their oncogenicity [1]. Here we report the synthesis and caging of cysteine in peptides that are substrates of the enzyme protein farnesyltransferase (PFTase). The photoremovable groups bromohydroxy quinoline (BHQ) and bromohydroxy coumarin (bhc) were incorporated into peptides using standard Fmoc SPPS and evaluated for their ability to release uncaged peptide upon photolysis. Kinetic analysis shows that BHQ and bhc uncaging of thiols is significantly more rapid compared to nitrobenzyl-based groups [2,3] although BHQ photolysis results in other photoproducts that reduce the overall efficiency. In addition we show that a bhc-caged peptide is not a substrate for PFTase, but upon irradiation such a peptide is famesylated by the enzyme.