Is the monomeric prion octapeptide repeat PHGGGWGQ a specific ligand for Cu2+ ions?

Abstract

Ac-PHGGGWGQ-NH₂, an octarepeat peptide fragment of prion, is a relatively effective ligand for Cu²⁺ ions. At a pH of about 7.4 the major binding sites involve the imidazole nitrogen and two amide nitrogens of ³Gly and ⁴Gly giving a CuH₋₂L species. The stability of the complex formed is similar to other peptides having a similar type of coordination. The NMR spectra indicate that in CuH₋₂L the complex side chain of the Trp residue is located very close to the metal ion. The geometry around the Cu²⁺ ion seems to be slightly distorted from the tetragonal one. In strongly basic solution the coordination involves an additional amide nitrogen. In CuH₋₂L, CuH₋₃L and CuH₋₄L complexes the amide nitrogens involved in the metal ion binding are those placed towards the C-terminal from the His residue. The N-terminal of the unprotected octapeptide is very effective in binding the Cu²⁺ ion although at high pH the imidazole nitrogen may not be involved in metal ion binding.