Protected natural peptides as intermediates for preparing semisynthetic peptides and protein analogs Selective acylation of ϵ-amino groups in cyanogen bromide peptides of cytochrome c using azidoformates

Abstract

Treatment of CNBr peptides 66–80, 81–104 and 66–104 from cytochrome c with t-butyloxycarbonyl azide leads to selective acylation of the ϵ-amino groups of lysine residues and the phenolic hydroxyl groups of tyrosine residues with less than 25% acylation of the α-amino groups. Similar selectivity was obtained for reactions of benzyloxycarbonyl azide, p-nitrobenzyloxycarbonyl azide and p-methoxybenzyloxycarbonyl azide with peptide 81–104. All of these protective groups can be removed under mild conditions, and thus, the partially protected natural peptides are desirable intermediates for the preparation of semisynthetic peptides. Model condensation reactions of N α t-butyloxycarbonyl methionine N-hydroxysuccinimide ester with Z-protected peptide 81–104 produced a peptide corresponding to residues 80 to 104 of cytochrome c in 94% yield.