T. Kowalik-jankowska et al., Cu(II) interaction with N-terminal fragments of human and mouse beta-amyloid peptide, J INORG BIO, 86(2-3), 2001, pp. 535-545
The stoichiometry, stability constants and solution structure of the comple
xes formed in the reaction of copper(II) with N-terminal fragments of human
and mouse beta -amyloid peptide, 1-6, 1-9, 1-10 have been determined by po
tentiometric, UV/VIS, CD and EPR spectroscopic methods. The fragments 1-9 a
nd 1-10 form complexes with the same coordination modes as the fragments 1-
6. The coordination of the metal ion for human and mouse fragments starts f
rom the N-terminal Asp residue which stabilizes significantly the IN comple
x as a result of chelation through the beta -carboxylate group. In a wide p
H range of 4-10, the imidazole nitrogen of His(6) is coordinated to form a
macrochelate. Results show that, in the pH range 5-9 the human fragments fo
rm the complex with different coordination mode compared to that of the mou
se fragments. The low pK(1) (amide) values (similar to5) obtained for the m
ouse fragments may suggest the coordination of the amide nitrogen of His wh
ile in case of the human fragments the coordination of the amide nitrogen o
f Ala(2) is suggested. The replacement of glycine by the arginine residue i
n the fifth position of the P-amyloid peptide sequence changes the coordina
tion modes of a peptide to metal ion in the physiological pH range. In a wi
de pH (including physiological) range the mouse fragments of beta -amyloid
peptide are much more effective in Cu(II) binding than the human fragments.
(C) 2001 Elsevier Science BY All rights reserved.