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

C. Kállay, Ildikó Turi, Sarolta Timári, Zoltán Nagy, Daniele Sanna, Giuseppe Pappalardo, Paolo De Bona, Enrico Rizzarelli, I. Sóvágó

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish
Title of host publicationMetal Ions in Neurological Systems
PublisherTUT Press
Pages189-197
Number of pages9
Volume9783709110010
DOIs
Publication statusPublished - 2012

Fingerprint

Peptide Fragments
Point Mutation
Copper
Metals
Peptides
Electron Spin Resonance Spectroscopy
Circular Dichroism
Histidine
Amides
Binding Sites
Ions
Oxygen
Amino Acids
Mutation
Prion Proteins

Keywords

  • Bioinorganic chemistry
  • Metal complexes
  • Peptides
  • Prion proteins

ASJC Scopus subject areas

  • Medicine (miscellaneous)

Cite this

Kállay, C., Turi, I., Timári, S., Nagy, Z., Sanna, D., Pappalardo, G., ... Sóvágó, I. (2012). The effect of point mutations on copper(II) complexes with peptide fragments encompassing the 106-114 region of human prion protein. In Metal Ions in Neurological Systems (Vol. 9783709110010, pp. 189-197). TUT Press. https://doi.org/10.1007/978-3-7091-1001-0_16

The effect of point mutations on copper(II) complexes with peptide fragments encompassing the 106-114 region of human prion protein. / Kállay, C.; Turi, Ildikó; Timári, Sarolta; Nagy, Zoltán; Sanna, Daniele; Pappalardo, Giuseppe; De Bona, Paolo; Rizzarelli, Enrico; Sóvágó, I.

Metal Ions in Neurological Systems. Vol. 9783709110010 TUT Press, 2012. p. 189-197.

Research output: Chapter in Book/Report/Conference proceedingChapter

Kállay, C, Turi, I, Timári, S, Nagy, Z, Sanna, D, Pappalardo, G, De Bona, P, Rizzarelli, E & Sóvágó, I 2012, The effect of point mutations on copper(II) complexes with peptide fragments encompassing the 106-114 region of human prion protein. in Metal Ions in Neurological Systems. vol. 9783709110010, TUT Press, pp. 189-197. https://doi.org/10.1007/978-3-7091-1001-0_16
Kállay C, Turi I, Timári S, Nagy Z, Sanna D, Pappalardo G et al. The effect of point mutations on copper(II) complexes with peptide fragments encompassing the 106-114 region of human prion protein. In Metal Ions in Neurological Systems. Vol. 9783709110010. TUT Press. 2012. p. 189-197 https://doi.org/10.1007/978-3-7091-1001-0_16
Kállay, C. ; Turi, Ildikó ; Timári, Sarolta ; Nagy, Zoltán ; Sanna, Daniele ; Pappalardo, Giuseppe ; De Bona, Paolo ; Rizzarelli, Enrico ; Sóvágó, I. / The effect of point mutations on copper(II) complexes with peptide fragments encompassing the 106-114 region of human prion protein. Metal Ions in Neurological Systems. Vol. 9783709110010 TUT Press, 2012. pp. 189-197
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AU - Timári, Sarolta

AU - Nagy, Zoltán

AU - Sanna, Daniele

AU - Pappalardo, Giuseppe

AU - De Bona, Paolo

AU - Rizzarelli, Enrico

AU - Sóvágó, I.

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N2 - 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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BT - Metal Ions in Neurological Systems

PB - TUT Press

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