SOLUTION-PHASE SYNTHESIS OF AN ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS PEPTIDE, T22 ([TYR(5,12),LYS(7)]-POLYPHEMUSIN-II), AND THE MODIFICATION OFTRP BY THE P-METHOXYBENZYL GROUP OF CYS DURING TRIMETHYLSILYL TRIFLUOROMETHANESULFONATE DEPROTECTION

T22 ([Tyr(5,12), Lys(7)]-polyphemusin II) was previously synthesized b y a solid-phase method and was found to have a strong anti-human immun odeficiency virus (HIV) activity, comparable to that of 3'-azido-2',3' -dideoxy-thymidine (AZT). In the present study, the solution-phase syn thesis of T22 was attempted in order to produce this peptide on a larg e scale. An 18-residue peptide amide corresponding to the entire amino acid sequence of T22 was synthesized by assembling four peptide fragm ents and two amino acid derivatives, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf ) in trifluoroacetic acid followed by air-oxidation. During this depro tection, a significant by-product derived from the transfer of the p-m ethoxybenzyl (MBzl) group from the sulfhydryl group of the cysteine re sidue to the side chain of the tryptophan residue was formed. This sid e reaction was found to be efficiently suppressed by adopting a two-st ep deprotection procedure using silver trifluoromethanesulfonate (AgOT f)-TMSOTf or trimethylsilyl bromide (TMSBr)-TMSOTf.