Copper(II) binding modes in the prion octapeptide PHGGGWGQ: a spectroscopic and voltammetric study.
The N-terminal octapeptide repeat region of human prion protein (PrPc) is known to bind Cu(II). To investigate the binding modes of copper in PrPc, an octapeptide Ac-PHGGGWGQ-NH2 (1), which corresponds to an octa-repeat sequence, and a tetrapeptide Ac-HGGG-NH2 (2) have been synthesised. The copper(II) complexes formed with 1 and 2 have been studied by circular dichroism (CD) and electron spin resonance (ESR) spectroscopy. Both peptides form 1:1 complexes with Cu(II) at neutral and basic pH. CD, ESR and visible absorption spectra suggest a similar co-ordination sphere of the metal ion in both peptides, which at neutral pH consists of a square pyramidal geometry with three peptidic nitrogens and the imidazole nitrogen as donor atoms. Cyclic voltammetric measurements were used to confirm the geometrical features of these copper(II) complexes: the observation of negative redox potentials are in good agreement with the inferred geometry. All these results taken together suggest that peptide 1 provides a single metal binding site to which copper(II) binds strongly at neutral and basic pH and that the binding of the metal induces the formation of a stiffened structure in the HGGG peptide fragment.
Bonomo
R P
RP
Dipartimento di Scienze Chimiche, Università di Catania, Italy. rbonomo@dipchi.unict.it
Imperllizzeri
G
G
Pappalardo
G
G
Rizzarelli
E
E
Tabbì
G
G
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*
D009842:Oligopeptides; D011328:Prions; D003300:Copper