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Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA
Address for correspondence: Christian Schöneich, Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Avenue, Lawrence, KS 66047. Voice: 785-864-4880; fax: 785-864-5736. schoneic{at}ukans.edu Ann. N.Y. Acad. Sci. 1012: 164-170 (2004).
This review summarizes tandem mass spectrometric investigations on the selectivity of metal-catalyzed oxidation of ß-amyloid peptide (ßAP) 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 ßAP1-40 to predominantly Tyr oxidation in the nonneurotoxic reverse sequence ßAP40-1. Within ßAP1-40, His13 and His14 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 ßAP-Cu2+ complex, lowering the incidence of ßAP-Cu2+-dependent Fenton-type reactions for the benefit of surrounding biological tissue.
Key Words: Alzheimer's disease • ascorbate • ß-amyloid peptide (ßAP) • Cu2+ • oxidation • sequence
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