Cyanogen bromide treatment of methionine-containing compounds

Abstract

The preparation of a series of X-Met-Gly-OEt and X-Met-Phe-OMe and their treatment with CNBr in either 70% or 97-100% formic acid at 25 degrees C are described where X is methanesulfonyl (mesyl), p-nitrobenzyloxycarbonyl, phthaloyl, trifluoroacetyl, acetyl, formyl, or tert-butyloxycarbonyl. Total cleavage of the peptide esters was found with mesyl-, p-nitrobenzyloxycarbonyl-, phthaloyl-, and trifluoroacetylmethionyl derivatives which indicated the suitability of these derivatives as amino protecting groups in peptide synthesis. Treatment of the acetylmethionyl peptide esters with CNBr in 70 and 97-100% formic acid resulted in 92 and 98% cleavage, respectively. With formylmethionyl peptide esters, about 85-95% cleavage was estimated when either 70 or 97-100% formic acid was used as the solvent. With the tert-butyloxycarbonylmethionyl derivatives, CNBr treatment in 70% formic acid resulted in about 93% cleavage of peptides, while treatment in 97-100% formic acid led to only 30-33% release of C-terminal amino acid esters. Quantitative cleavage of the carbonylbis(methionyl peptide esters) was observed. The reaction of CNBr with N-terminal methionyl derivatives containing free alpha-amino groups revealed that free methionine was quantitatively converted to homoserine lactone, whereas methionine ethyl ester and methionyl peptides (Met-Gly and Met-Phe) disappeared from the reaction mixture in 70% formic acid with only partial splitting of the ester (16%) or peptide bond (45%).