Elucidation of a novel polypeptide cross-link involving 3-hydroxykynurenine.

摘要: 3-Hydroxykynurenine, a metabolite of tryptophan, is powerful antioxidant and neurotoxin. The neurotoxicity results from the oxidation 3-hydroxykynurenine, hydroxyl radicals, formed via H(2)O(2), may also be implicated [Okuda, S., Nishiyama, N., Saito, H. , Katsuki, (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 12553-12558]. Oxidation o-aminophenols, such as in formation highly reactive quinonimines. Thus, one possible consequence 3-hydroxykynurenine covalent modification cellular macromolecules. Such process could contribute to potentially important other tissues, human lens, where functions UV filter. In this work, we demonstrate that can bind protein amino groups and, further, under oxidative conditions, function cross-link polypeptide chains. structure cross-linked moiety, using peptide glycyllysine, has been elucidated. cross-link, which both colored fluorescent, involves alpha-amino groups. Proteins modified by become fluorescent well cross-linked. LC-MS studies indicate present gamma-crystallin, following incubation lens presence 3-hydroxykynurenine. Similar posttranslational modifications proteins accompany cataract formation, knowledge precise mode reaction with will assist determining if involved degenerative conditions aminophenols implicated.