Acid-labile protecting groups for the synthesis of lipidated peptides

Lipidated peptides and their neolipoprotein derivatives are efficient tools for the investigation of biological processes in molecular detail. These compounds are often acid- and base-labile, and their synthesis requires the use of a combination of blocking groups that can be removed under very mild conditions. In this article we demonstrate that the Boc urethane and different trityl-type protecting groups can be cleaved selectively under acidic conditions that are mild enough to be compatible with the demands of lipopeptide synthesis. Thus, the Boc group was cleaved with TMS triflate in the presence of lutidine, and the methyltrityl (Mtt) and the methoxytrityl (Mmt) group were removed with 1% TFA in dichloromethane in the presence of triethylsilane as cation scavenger. Removal of the phenylfluorenyl group was achieved with up to 3% TFA in dichloromethane in the presence of triethylsilane at 0 degrees C. These protecting-group techniques were successfully applied in the synthesis of differently lipidated H-Ras peptides.