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Binding of TCA to the Prion Protein : Mechanism, Implication for Therapy, and Application as Probe for Complex Formation of Bio-macromolecules

Title data

Mangels, Christian ; Frank, Andreas ; Ziegler, Jan ; Klingenstein, R. ; Schweimer, Kristian ; Willbold, Dieter ; Korth, Carsten ; Rösch, Paul ; Schwarzinger, Stephan:
Binding of TCA to the Prion Protein : Mechanism, Implication for Therapy, and Application as Probe for Complex Formation of Bio-macromolecules.
In: Journal of Biomolecular Structure & Dynamics. Vol. 27 (2009) . - pp. 163-170.
ISSN 0739-1102

Abstract in another language

Tricyclic aromatic compounds (TCA) are promising candidates for treatment of transmissible spongiform encephalopathies. Direct binding to the cellular prion protein (PrP(C)) has been proposed as anti-prion active mechanism. We here show by means of NMR-spectroscopy that binding of TCA occurs with millimolar affinity to motifs consisting of two neighboring aromatic residues (Ar-Ar motif). It is independent of the secondary structure of this motif and of the side chain attached to the TCA and it is not specific to PrP(C). Because biologically inactive 9-aminoacridine (9-aa) binds with similar K(D) as anti-prion active quinacrine, direct interaction with PrP(C) as mechanism of action appears highly unlikely. However, binding of 9-aa to Ar-Ar-motifs in proteins can be used as reporter for biological macromolecule interactions, by measuring changes in T(1)-NMR relaxation times of 9-aa.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biopolymers
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Biopolymers - Univ.-Prof. Dr. Paul Rösch
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Result of work at the UBT: Yes
DDC Subjects: 500 Science
500 Science > 500 Natural sciences
500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 19 Dec 2014 14:10
Last Modified: 30 Jan 2019 06:53
URI: https://eref.uni-bayreuth.de/id/eprint/5320