Nonenzymatic cleavage of tryptophyl peptide bonds in peptides and proteins: I. Cleavage of C-tryptophyl peptide bonds in model peptides through their conversion into N′-formylkynurenine derivatives

Abstract

Procedures for effecting specific cleavage of tryptophanyl peptide bonds of proteins have been intensively sought in the past decade. The reagents tested in such procedures include periodate, ozone, and in particular brominating agents. N-Bromosuccinimide (NBS) was the first reagent proposed for the cleavage of tryptophanyl peptide bonds, but various side reactions of this extremely reactive reagent with other amino acid side chains, as well as poor yields in peptide bond fission, hampered practical applications of the reagent. 2,4,6-Tribromo-4-methylcyclohexadienone is found to be less reactive than NBS, giving similar yields of cleavage, but extensive modification of tyrosine, histidine, and sulfur amino acids is observed in this case. Positive halogen reagents, such as ICl, iodide oxidized with Chloramine-T, N-iodosuccinimide, and active iodine generated with H2O2, iodide, and a peroxidase, also give moderate yields of cleavage. A mixture of dimethyl sulfoxide (DMSO) and concentrated aqueous HBr has been recently used as a brominating agent to effect selective cleavage of tryptophanyl peptide bonds in peptides and proteins.