Amino Acids

, Volume 44, Issue 5, pp 1279–1292 | Cite as

Quinacrine reactivity with prion proteins and prion-derived peptides

  • Zbigniew Zawada
  • Martin Šafařík
  • Eva Dvořáková
  • Olga Janoušková
  • Anna Březinová
  • Ivan Stibor
  • Karel Holada
  • Petr Bouř
  • Jan Hlaváček
  • Jaroslav Šebestík
Original Article

Abstract

Quinacrine is a drug that is known to heal neuronal cell culture infected with prions, which are the causative agents of neurodegenerative diseases called transmissible spongiform encephalopathies. However, the drug fails when it is applied in vivo. In this work, we analyzed the reason for this failure. The drug was suggested to “covalently” modify the prion protein via an acridinyl exchange reaction. To investigate this hypothesis more closely, the acridine moiety of quinacrine was covalently attached to the thiol groups of cysteines belonging to prion-derived peptides and to the full-length prion protein. The labeled compounds were conveniently monitored by fluorescence and absorption spectroscopy in the ultraviolet and visible spectral regions. The acridine moiety demonstrated characteristic UV–vis spectrum, depending on the substituent at the C-9 position of the acridine ring. These results confirm that quinacrine almost exclusively reacts with the thiol groups present in proteins and peptides. The chemical reaction alters the prion properties and increases the concentration of the acridine moiety in the prion protein.

Keywords

Quinacrine Prion protein and peptide model reactions Solid phase and recombinant synthesis 

Notes

Acknowledgments

This work was supported by the Czech Science Foundation (GA CR) Grant No. 203/07/1517. KH, OJ and ED were supported by the projects of Charles University in Prague: PRVOUK-P24/LF1/3, UNCE 204022 and SVV-2012- 264506. English language revision was made by American Journal Experts, http://www.journalexperts.com.

Conflict of interest

Authors declare that they have no conflict of interest.

Supplementary material

726_2013_1460_MOESM1_ESM.doc (1.1 mb)
Supplementary material 1 (DOC 1149 kb)

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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Zbigniew Zawada
    • 1
    • 2
  • Martin Šafařík
    • 1
  • Eva Dvořáková
    • 3
  • Olga Janoušková
    • 3
  • Anna Březinová
    • 1
  • Ivan Stibor
    • 1
    • 4
  • Karel Holada
    • 3
  • Petr Bouř
    • 1
  • Jan Hlaváček
    • 1
  • Jaroslav Šebestík
    • 1
  1. 1.Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech RepublicPrague 6Czech Republic
  2. 2.Institute of Chemical TechnologyPrague 6Czech Republic
  3. 3.First Faculty of MedicineCharles University in PraguePrague 2Czech Republic
  4. 4.Technical University of LiberecLiberec 1Czech Republic

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