ORGN 38 |
| Lawrence M. Sayre and Ke-Qing Ling. Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106 |
| The copper amine oxidases convert primary unbranched amines to aldehydes at the expense of reducing oxygen to hydrogen peroxide. The amine deamination half-reaction is mediated by one of two different quinone cofactors derived by oxidation of an active-site tyrosine, wherein either water or an active-site lysine adds to the initially formed ortho-quinone intermediate to give ultimately a 2,4,6-trihydroxyphenylalanine quinone (TPQ) or the cross-linked lysine tyrosylquinone (LTQ), respectively. Here we describe the synthesis of models with the goal of establishing chemical precedent for the overall six-electron oxidation processes needed to generate TPQ and LTQ. The LTQ model invokes an intramolecular cyclization of a pendant amine group at the ortho-quinone stage. For TPQ, since the key water addition step is proposed to involve the catalytic influence of the active site copper, the model in this case incorporates a pendant copper-coordinating ligand into the quinone precursor. Oxidation of the corresponding catechol is found to generate the TPQ-like product at neutral pH only in the presence of Cu(II). |
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Lipids, Biosynthesis, Enzyme Inhibitors, and Mimetics
8:00 AM-11:40 AM, Sunday, September 7, 2003 Sheraton New York -- Royal Ballroom B, Oral
Division of Organic Chemistry |