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 (PAP) and related sequences. A remarkable feature of the Cu2+/ascorbate-dependent oxidation of these peptides is the switch from predominantly His oxidation in the neurotoxic peptide betaAPl-40 to predominantly Tyr oxidation in the nonneurotoxic reverse sequence betaAP40-1. Within betaAPI-40, His(13) and His(14) of the high-affinity Cu2+-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-Cu2+ complex, lowering the incidence of betaAP-Cu2+-dependent Fenton-type reactions for the benefit of surrounding biological tissue.