Effective use of free thiols as scavengers for HF cocktails to deprotect bromo- and chloroacetylated synthetic peptides.

Abstract

A variety of thiol-containing compounds, in combination with m-cresol, were tested as scavengers in hydrogen fluoride (HF) cocktails that are used to deprotect haloacetylated peptidyl resins. Our results indicate that brome and chloroacetyl moieties on a synthetic peptide remain intact following HF treatment when the HF cocktail contains m-cresol along with either thiophenol, m-thiocresol or 1,2-ethanedithiol. The free thiols prevent the formation of a number of impurities in the preparation of bromo- and chloroacetylated peptides that contain amino acids that could be oxidized in a nonreducing HF environment. Ethvimethylsulfide, however, could not be used with bromoacetylated peptides, but it could be used with chloroacetylated peptides.