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.
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.
Schöneich
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Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Avenue, Lawrence, KS 66047, USA. schoneic@ukans.edu
Williams
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D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D014443:Tyrosine / Q000737:chemistry
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C090308:amyloid beta-protein (40-1); D014443:Tyrosine; D010649:Phenylalanine; D006639:Histidine; D003300:Copper