at Google ScholarTitle 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)
Issue 2
.
- pp. 163-170.
ISSN 1538-0254
DOI: https://doi.org/10.1080/07391102.2009.10507306
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.