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Cell Mol Biol (Noisy-le-grand). 2003 Jul;49(5):753-61.

CU(II)-catalyzed oxidation of Alzheimer's disease beta-amyloid peptide and related sequences: remarkably different selectivities of neurotoxic betaAP1-40 and non-toxic betaAP40-1.

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1
Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Avenue, Lawrence, KS 66047, USA. schoneic@ukans.edu

Abstract

We investigated the CuII-catalyzed oxidation of beta-amyloid peptides betaAP10-20 and betaAP40-1 by tandem mass spectrometry and compared oxidation yields and selectivities to those for betaAP1-16, betaAP1-28 and betaAP1-40, which were obtained earlier (26). While betaAP1-16, betaAP1-28 and betaAP1-40 showed an almost exclusive oxidation of His residues to 2-oxo-histidine, the selectivity pattern is changed for betaAP10-20,which shows oxidation of His but also hydroxylation of Tyr and Phe. In contrast to betaAP1-40, the reverse sequence betaAP40-1 shows a strong selectivity for the hydroxylation of Tyr31 while only negligible His oxidation is observed at early time points. These selectivity patterns show the importance of the geometry of the metal-binding site for peptide/protein oxidation. The significantly different characteristic of betaAP1-40 and betaAP40-1 with regard to metal catalyzed processes may be related to the differences in the neurotoxic properties of these sequences.

PMID:
14528912
[Indexed for MEDLINE]

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