Copper(II) Binding Modes in the Prion Octapeptide PHGGGWGQ: A Spectroscopic and Voltammetric Study
- 31 October 2000
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 6 (22) , 4195-4202
- https://doi.org/10.1002/1521-3765(20001117)6:22<4195::aid-chem4195>3.0.co;2-2
Abstract
The N-terminal octapeptide repeat region of human prion protein (PrPc) is known to bind CuII. To investigate the binding modes of copper in PrPc, an octapeptide Ac-PHGGGWGQ-NH2 (1), which corresponds to an octarepeat 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 CuII 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.Keywords
This publication has 59 references indexed in Scilit:
- Synthesis, Spectroscopic Characterisation, and Metal Ion Interaction of a Newα-Helical PeptideChemistry – A European Journal, 1998
- Co-ordinating properties of cyclopeptides. Thermodynamic and spectroscopic study on the formation of copper(II) complexes with cyclo(Gly-His)4 and cyclo(Gly-His-Gly)2 and their superoxide dismutase-like activityJ. Chem. Soc., Dalton Trans., 1998
- Copper(II) complexes with cyclo(L-aspartyl-L-aspartyl) and cyclo(L-glutamyl-L-glutamyl) derivatives and their antioxidant propertiesJ. Chem. Soc., Dalton Trans., 1996
- Templates That Induce .alpha.-Helical, .beta.-Sheet, and Loop ConformationsChemical Reviews, 1995
- Co-ordination properties of cyclopeptides. Formation and stability of zinc(II) and copper(II) complexes of histidine-containing cyclopeptides, or imidazoleJ. Chem. Soc., Dalton Trans., 1994
- Thermodynamic and spectroscopic characterization and in vitro O2 ? scavenger activity of copper(II) glycyl-L-histidyl-glycyl-L-histidine complexesJ. Chem. Soc., Dalton Trans., 1993
- Protein Stabilization by Engineered Metal ChelationBio/Technology, 1991
- Thermodynamic stereoselectivity assisted by weak interactions in metal complexes. Copper(II) ternary complexes of cyclo-L-histidyl-L-histidine and L- or D-amino acids in aqueous solutionJ. Chem. Soc., Dalton Trans., 1991
- De novo design of a Zn2+-binding proteinJournal of the American Chemical Society, 1990
- Coordination properties of cyclopeptides. Formation, stability, and structure of proton and copper(II) complexes of cyclo-(L-histidyl-L-histidyl) in aqueous solutionInorganic Chemistry, 1987