Copper(II) complexation by human and mouse fragments (11-16) of beta-amyloid peptide

A potentiometric and spectroscopic (UV-Vis, CD, NMR and EPR) study of coppe r(II) bonding to the N-terminal (11-16) of human and mouse fragments of bet a -amyloid peptide (EVHHQK-NH2, EVRHQK-NH2 and their N-blocked derivatives) was performed. The results indicate that the hexapeptide amide EVHHQK-NH2 forms in the pH range 4.5-10.5 complexes in which the coordination of coppe r(II) is typical {NH2, 2N(-), N-Im} for the peptide sequence Xaa-Yaa-His. T he mouse fragment containing the N-terminal amino group free in a wide pH r ange is coordinated through the terminal amino group, carbonyl oxygen or on e or two deprotonated amide nitrogens from the N-termini, while the fourth coordination site is occupied by a nitrogen donor of imidazole in the form of a macrochelate. When the amino group is blocked (Ac-EVRHQK-NH2) the imid azole nitrogen of the histidine residue acts as an anchoring bonding site a nd at higher pH the 3N and 4N complexes are formed with the amide nitrogens coordinated. A blocked hexapeptide modeling a part of human beta -amyloid peptide (Ac-EVHHQK-NH2) forms complexes with coordination through imidazole nitrogens both of histidine residues over a broad pH range. With increasin g pH the amide nitrogens are also coordinated. In a wide pH range including physiological, Ac-EVHHQK-NH2 (human fragment) is much more effective in co pper(II) ion bonding than is Ac-EVRHQK-NH2 (mouse fragment).