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The effect of point mutations on copper(II) complexes with peptide fragments encompassing the 106–114 region of human prion protein

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Abstract

The tetrapeptides Ac-SKHM-NH2, Ac-TKHM-NH2, Ac-MKHS-NH2, Ac-S(OMe)KHM-NH2, and Ac-MKHS(OMe)-NH2 and the nonapeptides Ac-KTNSKHMAG-NH2 and Ac-KTNMKHSAG-NH2 were synthesized and their copper(II) complexes were studied by potentiometric, UV–Vis, circular dichroism (CD), and electron paramagnetic resonance (EPR) spectroscopic methods. These peptides mimic the 109–112 and 106–114 residues of the sequence of human prion protein. The imidazole-N donor atoms of histidyl residues were found to be the primary metal binding sites of all peptide fragments. This binding mode provides a good possibility for the cooperative deprotonation and metal ion coordination of two amide functions preceding histidine. The (Nim,N−,N−)-bonded species predominate in the pH range 5.5–7.0 and the free coordination sites of these species make possible the metal binding of weakly coordinating side chains. The comparison of the potentiometric and spectroscopic results revealed the stabilizing role of the oxygen donors of seryl, threonyl, or methoxyseryl residues of Ac-SKHM-NH2, Ac-TKHM-NH2, Ac-S(OMe)KHM-NH2, and Ac-KTNSKHMAG-NH2 containing the mutations in position 109. These interactions were, however, not observed in the peptides containing the specific amino acids in other locations of the peptide sequence.

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Acknowledgments

This work was supported by the MTA(Hungary)-CNR(Italy) bilateral program and the research grant OTKA-NKTH 77586, OTKA 72956 and PD 72321 and TAMOP 4.2.1/B-09/1/KONV-2010-0007 (Hungary).

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Authors and Affiliations

  1. Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen, 4010, Hungary

    Csilla Kállay, Ildikó Turi, Sarolta Timári & Imre Sóvágó

  2. Department of Colloid Chemistry, University of Debrecen, Debrecen, 4010, Hungary

    Zoltán Nagy

  3. CNR Institute of Biomolecular Chemistry, Traversa La Crucca 3, 07040, Baldinca-Li Punti (Sassari), Italy

    Daniele Sanna

  4. CNR Institute of Biostructures and Bioimagining, V.le A. Doria 6, 95125, Catania, Italy

    Giuseppe Pappalardo & Enrico Rizzarelli

  5. Department of Chemical Sciences, University of Catania, V.le A. Doria 6, 95125, Catania, Italy

    Paolo de Bona & Enrico Rizzarelli

Authors
  1. Csilla Kállay
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  2. Ildikó Turi
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  3. Sarolta Timári
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  4. Zoltán Nagy
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  5. Daniele Sanna
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  6. Giuseppe Pappalardo
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  7. Paolo de Bona
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  8. Enrico Rizzarelli
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  9. Imre Sóvágó
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Correspondence to Imre Sóvágó.

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Kállay, C., Turi, I., Timári, S. et al. The effect of point mutations on copper(II) complexes with peptide fragments encompassing the 106–114 region of human prion protein. Monatsh Chem 142, 411–419 (2011). https://doi.org/10.1007/s00706-010-0413-2

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  • DOI: https://doi.org/10.1007/s00706-010-0413-2

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