Practical Protein Chemistry - A. Darbre 1989

Polypeptide Fragmentation by Chemical Methods
Other Methods of Chemical Cleavage of Peptide Bonds
Cleavage at Histidine Residue

The double bond at the γ–δ position of the Histidine imidazole ring is essentially analogous to the double bond found in Tryptophan and Tyrosine residues. In practice, Peptides are cleaved at histidine residues by the action of N-Bromosuccinimide, albeit with a lower yield than for tryptophan [170, 171]. The putative reaction mechanism presumably involves The formation of a five-membered iminolactone intermediate, which readily hydrolyzes in an acidic environment, analogous to the Cleavage of peptides at tryptophan and tyrosine residues [181]. The cleavage of histidine-containing peptides with N-bromosuccinimide is carried out in a pyridine-acetate buffer (pH 3) at 100°C for 1 h.

To preclude Cleavage at tryptophan and tyrosine residues, tyrosine residues are O-acylated [170] and tryptophan residues are selectively alkylated using 2-hydroxy-5-nitrobenzyl bromide [206]. Due to poor yields and the side-chain oxidation of Certain Amino Acids, particularly sulfur-containing ones, this approach is rarely utilized for the fragmentation of Proteins AND PEPTIDES.