Model Studies on the Metal-Catalyzed Protein Oxidation: Structure of a Possible His-Lys Cross-Link

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• 作者：Yahua Liu ; Gang Sun ; Adrian David ; and Lawrence M. Sayre
• 刊名：Chemical Research in Toxicology
• 出版年：2004
• 出版时间：January 2004
• 年：2004
• 卷：17
• 期：1
• 页码：110 - 118
• 全文大小：145K
• 年卷期：v.17,no.1(January 2004)
• ISSN：1520-5010

文摘

Redox active transition metals such as copper and iron contribute to biomacromoleculardamage that occurs during oxidative stress in a number of degenerative disorders and resultsin protein cross-linking. On the basis of suggestive evidence for an oxyradical-induced cross-linking between His and Lys side chains, we investigated the Cu(II)-catalyzed oxidation of4-alkylimidazoles in the presence of amines, as surrogates for these amino acid side chains,using ascorbic acid as a continual source of reducing equivalents. A model His-Lys cross-linkwas isolated and structurally characterized as a 5-alkyl-5-hydroxy-4-(alkylamino)-1,5-dihydroimidazol-2-one by NMR and mass spectrometry. Evidence that the 2-imidazolone, theprincipal oxidation product found in the absence of amine, is an intermediate in the formationof the imidazole-amine adduct was that higher yields of the cross-link adduct were obtainedstarting with the 2-imidazolone. Possible mechanisms for formation of the cross-link and otherobserved products are discussed.