EFFECTIVE USE OF FREE THIOLS AS SCAVENGERS FOR HF COCKTAILS TO DEPROTECT BROMOACETYLATED AND CHLOROACETYLATED SYNTHETIC PEPTIDES

A variety of thiol-containing compounds, in combination with m-cresol, were tested as scavengers in hydrogen fluoride (HF) cocktails that ar e used to deprotect haloacetylated peptidyl resins. Our results indica te that bromo- 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 f ree thiols prevent the formation of a number of impurities in the prep aration of bromo- and chloroacetylated peptides that contain amino aci ds that could be oxidized in a nonreducing HF environment. Ethylmethyl sulfide, however, could not be used with bromoacetylated peptides, but it could be used with chloroacetylated peptides.