Coordination abilities of the 1-16 and 1-28 fragments of β-amyloid peptide towards copper(II) ions:: a combined potentiometric and spectroscopic study

Stoichiometry, stability constants and solution structures of the copper(II) complexes of the (1-16H), (1-28H), (1-16M), (1-28M), (Ac-1-16H) and (Ac-1-16M) fragments of human (H) and mouse (M) P-amyloid peptide were determined in aqueous solution in the pH range 2.5-10.5. The potentiometric and spectroscopic data (UV-Vis, CD, EPR) show that acetylation of the amino terminal group induces significant changes in the coordination properties of the (Ac-1-16H) and (Ac-1-16M) peptides compared to the (1-16H) and (1-16M) fragments, respectively. The (Ac-1-16H) peptide forms the 3N {N-Im(6), N-Im(13), N-Im(14)} complex in a wide pH range (5-8), while for the (Ac-1-16M) fragment the 2N {N-Im(6), N-Im(14)} complex in the pH range 5-7 is suggested. At higher pH values sequential amide nitrogens are deprotonated and coordinated to copper(II) ions. The N-terminal amino group of the (1-16) and (1-28) fragments of human and mouse beta-amyloid peptide takes part in the coordination of the metal ion, although, at pH above 9 the complexes with the 4N {N-Im, 3N(-)} coordination mode are formed. The phenolate -OH group of the Tyr(10) residue of the human fragments does not coordinate to the metal ion. (C) 2003 Elsevier Science Inc. All rights reserved.