NON-ENZYMATIC CLEAVAGE OF HISTIDYL PEPTIDE BONDS

Abstract

This chapter discusses nonenzymatic cleavage of histidyl peptide bonds. Histidyl residues (I) have a double bond in the γ-δ position relative to the carbonyl group of the peptide bond. When histidyl peptides are treated with 3 moles of N-bromosuccinimide (NBS) in 50% aqueous acetic acid at room temperature, they are cleaved in 18–28% yield. However, if the reaction mixture is heated for 1 h at 100°, the yields rise to 50–65%. If the reaction with NBS is performed in a buffer of pyridine–acetic acid–water, almost no cleavage occurs at room temperature; however, on heating, 55–65% cleavage is obtained. In the pyridine acetate buffer, the water competes with the peptide bond for the bromonium ion initially formed and brings about rupture of the imidazole ring. As a result of this, α-ketoaldehyde, ammonia, and formamide are formed.