Copper(II) binding of prion protein's octarepeat model peptides

Abstract The complexes between copper(II) and the synthetic octapeptide fragments of the prion protein Ac-GWGQPHGG-NH 2 ( 1 ), Ac-PHGGGWGQ-NH 2 ( 3 ) and the cyclic analogue c-(GWGQPHGG) ( 2 ) have been comparatively investigated by circular dichroism (CD), absorption (UV–Vis), and electron paramagnetic resonance (EPR) spectroscopic methods. The results suggest a similar copper(II) coordination behaviour of the two linear peptides. In both cases two major complex species were spectroscopically detected. The first one, existing in the range of pH 7–9, showed spectroscopic parameters attributable to a 3N complex species, while the 4N complex was the main species at strongly alkaline pH values. Copper(II) binding appears to be confined within the aminoacid sequence HGG. Cyclisation of the main chain, as in the peptide 2 , was found to have remarkable effects on the copper(II) complex speciation especially at pH 7–8 where the 3N species predominated in the linear counterparts. By contrast the spectroscopic data obtained at pH 11 provided evidence of the restoration of the same set of donor atoms as in the linear peptides.