Copper complex species within a fragment of the N-terminal repeat region in opossum PrP protein

A spectroscopic (UV-Vis, CD and EPR), thermodynamic and voltammetric study of the copper(II)complexes with the Ac-PHPGGSNWGQ-NH2 polypeptide (L), a fragment of the opossum PrP proteinN-terminal four-repeat region, was carried out in aqueous solution. It suggests the formation of ahighly distorted [Cu(L)H-2] complex species in the neutral region, the stereochemistry of which isascribable to a square base pyramid and a CuN3O2 chromophore, resulting from the coordination of ahistidine imidazole and two peptide nitrogen atoms and probably oxygen atoms from water molecules.At basic pH values a [Cu(L)H-3]- species with a pseudo-octahedral geometry was also obtained, withfour nitrogen donor atoms in its equatorial plane, coming from the histidine residue and from peptidicnitrogen atoms. Interestingly, at pH values relatively higher than the neutrality, the coordination sphereof the copper complex in the [Cu(L)H-2] species changes its stereochemistry towards apseudo-octahedron, as suggested by the change in the parallel copper hyperfine coupling constant ofthe EPR spectra at low temperature. A slight difference in the redox potentials between this two-faced[Cu(L)H-2] complex species seems to confirm this behaviour. Both potentiometric and spectroscopicdata were compared with the analogous species obtained with the Ac-PHGGGWGQ-NH2 peptide,belonging to the octarepeat domain of the human prion protein (hPrP) N-terminal region. The[Cu(L)H-2] species formed by the Ac-PHPGGSNWGQ-NH2 decapeptide, having a slightly lowerstability, turned out to be less abundant and to exist within a narrow pH range