JBIC Journal of Biological Inorganic Chemistry

, Volume 10, Issue 5, pp 463–475 | Cite as

Copper(II) complexes with chicken prion repeats: influence of proline and tyrosine residues on the coordination features

  • Diego La Mendola
  • Raffaele P. Bonomo
  • Giuseppe Impellizzeri
  • Giuseppe Maccarrone
  • Giuseppe Pappalardo
  • Adriana Pietropaolo
  • Enrico Rizzarelli
  • Valeria Zito
Original Article


The prion protein (PrPc) is a copper-binding glycoprotein that can misfold into a β-sheet-rich and pathogenic isoform (PrPsc) leading to prion diseases. The first non-mammalian PrPc was identified in chicken and it was found to keep many structural motifs present in mammalian PrPc, despite the low sequence identity (approximately 40%) between the two primary structures. The present paper describes the synthesis and the coordination properties of some hexapeptide fragments (namely, PHNPGY , HNPGYP and NPGYPH) as well as a bishexapeptide (PHNPGYPHNPGY), which encompasses two hexarepeats. The copper(II) complexes were characterized by means of potentiometric, UV–vis, circular dichroism and electron paramagnetic resonance techniques. We also report the synthesis of three hexapeptides (PHNPGF, HNPGFP and NPGFPH), in which one tyrosine was replaced by phenylalanine as well as two bishexapeptides in which either one (PHNPGFPHNPGY and PHNPGYPHNPGF), or two tyrosines were replaced by phenylalanine, in order to check whether tyrosine was involved in copper(II) binding. Overall, the results indicate that the major copper(II) species formed by the chicken PrP dodecapeptides are stabler than the analogous species reported for the peptide fragments containing two octarepeat peptides from the mammalian prion protein. It is concluded that the presence of four prolyl residues, that are break points in copper coordination, induces the metal-assisted formation of macrochelates as well as the formation of binuclear species. Furthermore, it has been shown that the phenolic group is directly involved in the formation of copper binuclear species.


Prion Copper(II) complexes Tandem hexarepeats Tyrosine 



This work was in part supported by the University of Catania, CNR Rome, and MIUR (PRIN-2003031424 and grant no.196 D.M. 1105/2002).

Supplementary material

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Copyright information

© SBIC 2005

Authors and Affiliations

  • Diego La Mendola
    • 1
  • Raffaele P. Bonomo
    • 2
  • Giuseppe Impellizzeri
    • 2
  • Giuseppe Maccarrone
    • 2
  • Giuseppe Pappalardo
    • 1
  • Adriana Pietropaolo
    • 2
  • Enrico Rizzarelli
    • 1
    • 2
  • Valeria Zito
    • 1
  1. 1.Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle RicercheSezione di CataniaCataniaItaly
  2. 2.Dipartimento di Scienze ChimicheUniversità di CataniaCataniaItaly

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