title: Quinacrine reactivity with prion proteins and prion-derived peptides.
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.
authors: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
authors: Zbigniew
authors: Z
authors: Zawada
authors: Martin
authors: M
authors: Šafařík
authors: Eva
authors: E
authors: Dvořáková
authors: Olga
authors: O
authors: Janoušková
authors: Anna
authors: A
authors: Březinová
authors: Ivan
authors: I
authors: Stibor
authors: Karel
authors: K
authors: Holada
authors: Petr
authors: P
authors: Bouř
authors: Jan
authors: J
authors: Hlaváček
authors: Jaroslav
authors: J
authors: Sebestík
mesh_terms: D000166:Acridines / Q000737:chemistry; D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry; D011796:Quinacrine / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000166:Acridines; D010446:Peptide Fragments; D011328:Prions; D011796:Quinacrine; D003545:Cysteine