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.