Nickel(II) and mixed metal complexes of amyloid-beta N-terminus.
Nickel(II) complexes of Abeta(1-16)Y10A and its smaller fragments including Abeta(1-4), Abeta(1-6), Ac-Abeta(1-6) and Ac-Abeta(8-16)Y10A have been studied by potentiometric, UV-Vis and circular dichroism spectroscopic measurements. The formation of mixed metal complexes and the distribution of metal ions among the possible coordination sites in the Cu(II)-Ni(II)-Abeta(1-16)Y10A and Cu(II)-Ni(II)-Zn(ii)-Abeta(1-16)Y10A systems have also been evaluated. It was found that the hexadecapeptide and its fragments are effective nickel(II) binding ligands and complex formation processes of nickel(II) ions are quite similar to those of copper(II). Formation of mono- and di-nuclear complexes was detected in the nickel(II)-Abeta(1-16)Y10A system suggesting the existence of two separated metal binding motifs: the N-terminus and internal histidyl residues. The preference for the coordination at the N-terminus was supported by the spectroscopic measurements but in equilibrium with the metal binding at the internal histidyl sites. Neither zinc(II) nor nickel(II) can, however, substitute copper(II) in the mixed metal complexes of Abeta(1-16)Y10A, but both metal ions are able to alter the distribution of copper(II) ions among the various binding sites. Both N-terminus (amino and His6) and internal histidyl residues (His13 and His14) can work as dinuclear binding motifs, preferably accommodating copper(II) and zinc(II), respectively, while nickel(II) can occupy the remaining free coordination sites.
Józsa
Eva
E
University of Debrecen, Department of Inorganic and Analytical Chemistry, H-4010, Debrecen, Hungary.
Osz
Katalin
K
Kállay
Csilla
C
de Bona
Paolo
P
Damante
Chiara A
CA
Pappalardo
Giuseppe
G
Rizzarelli
Enrico
E
Sóvágó
Imre
I
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011199:Potentiometry; D015032:Zinc / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D009942:Organometallic Compounds; D003300:Copper; D009532:Nickel; D015032:Zinc