Selective Cu2+/ascorbate-dependent oxidation of alzheimer's disease beta-amyloid peptides.
This review summarizes tandem mass spectrometric investigations on the selectivity of metal-catalyzed oxidation of beta-amyloid peptide (betaAP) and related sequences. A remarkable feature of the Cu(2+)/ascorbate-dependent oxidation of these peptides is the switch from predominantly His oxidation in the neurotoxic peptide betaAP1-40 to predominantly Tyr oxidation in the nonneurotoxic reverse sequence betaAP40-1. Within betaAP1-40, His(13) and His(14) of the high-affinity Cu(2+)-binding site are most sensitive to oxidation. Eventually, the oxidation of one or both of these His residues could result in a less redox-active betaAP-Cu(2+) complex, lowering the incidence of betaAP-Cu(2+)-dependent Fenton-type reactions for the benefit of surrounding biological tissue.
Schöneich
Christian
C
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA. schoneic@ukans.edu
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D006900:Hydroxylation; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D017665:Hydroxyl Radical; D014443:Tyrosine; D006639:Histidine; D003300:Copper; D001205:Ascorbic Acid