Synthesis of palmitoyl-thioester T-cell epitopes of myelin proteolipid protein (PLP). Comparison of two thiol protecting groups (StBu and Mmt) for on-resin acylation

In order to test the effect of thiopalmitoylation on the encephalitognic pr operties of two proteolipid protein (PLP) T-cell epitopes, we have studied the on-resin S-palmitoylation of peptides, synthesized using the Fmoc/tBu s trategy. The use of two Cys protecting groups was investigated: Che tert-bu tyl-sulfenyl (StBu) and the methoxytrityl (Mmt). Our studies show that the ease of deprotection of the thiol protected with StBu was sequence dependen t. The deprotection of Cys(StBu) was difficult in the case of the two pepti des PLP(104-117) and PLP(139-151). Neither of the two Cys(StBu) (Cys(108) a nd Cys(140), respectively) could be deprotected with tributylphosphine. bet a-mercaptoethanol was only efficient for the deprotection of Cys(StBu)(140) at 85 degrees C and at 135 degrees C for Cys(108). The two palmitoylated p eptides could be obtained in good yield starting from Cys protected with Mm t. Our conclusion is that the Mmt group is the more versatile protecting gr oup of the thiol for use in the on-resin synthesis of thiopalmitoylated pep tides. Copyright (C) 2000 European Peptide Society and John Wiley & Sons, L td.