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Chem Res Toxicol. 2019 Mar 18;32(3):513-525. doi: 10.1021/acs.chemrestox.8b00363. Epub 2019 Feb 15.

Carnosine and Carcinine Derivatives Rapidly React with Hypochlorous Acid to Form Chloramines and Dichloramines.

Author information

1
The Heart Research Institute , Newtown , New South Wales 2042 , Australia.
2
Sydney Medical School , University of Sydney , Sydney , New South Wales 2006 , Australia.
3
Panum Institute , University of Copenhagen , Copenhagen 2200 , Denmark.
4
School of Molecular Sciences , The University of Western Australia , Perth , Western Australia 6009 , Australia.
5
School of Chemistry , University of Sydney , Sydney , New South Wales 2006 , Australia.

Abstract

Hypochlorous acid (HOCl) is a highly reactive, toxic species generated by neutrophils via the action of myeloperoxidase in order to destroy invading pathogens. However, when HOCl is produced inappropriately, it can damage host tissue and proteins and plays a role in the initiation and progression of disease. Carnosine, a peptide of β-alanine and histidine, has been shown to react rapidly with HOCl yielding monochloramines and can undergo intramolecular transchlorination. The current study examines the kinetics and pH dependence of the reactions of carnosine and novel structural derivatives with HOCl and the occurrence of intra- and intermolecular transchlorination processes. We demonstrate that the transchlorination reactions of carnosine are pH dependent, with intramolecular transfer favored at higher pH. Carcinine, having a structure identical to carnosine though lacking the carboxylic acid group of the histidine residue, reacts with HOCl and forms monochloramines though intramolecular transfer reactions are not observed, and this is supported by computational modeling. Novel analogues with one (carnosine+1) and two (carnosine+2) methylene groups in the alkyl chain of the β-alanine react with HOCl to yield monochloramines that undergo transchlorinations to yield a mixture of mono- and dichloramines. The latter are stable over 24 h. The ability of carnosine and derivatives to react rapidly with HOCl to give long-lived, poorly reactive, species may prevent damage to proteins and other targets at sites of inflammation.

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