NR AWJO
AU Mangels,C.; Frank,A.O.; Ziegler,J.; Leliveld,R.S.; Klingenstein,R.; Schweimer,K.; Reindl,W.; Willbold,D.; Korth,C.; Rösch,P.; Schwarzinger,S.
TI Quinacrine binding to proteins: mechanism, implications for anti-prion therapy and application as in vitro screening assay for PrP binding
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions THE-09
PT Konferenz-Poster
AB Tricyclic aromatic (TCA) compounds have been proposed to be candidates for treatment of TSE. Direct interaction with PrPc has been suggested as mechanism of drug action. We here show by means of NMR-spectroscopy that binding of TCA compounds occurs with millimolar kD to motifs consisting of two neighboring aromatic residues. Binding is independent of the secondary structure of the double-aromatic residue motif and independent of the side chains attached to the tricyclic aromatic compound and is not specific to PrP. Moreover, biologically inactive 9-aminoacridine (9-aa) binds with similar kD than anti-prion active quinacrine ruling out direct interaction of TCA's with PrPc as drug active mechanism. However, binding of 9-aa to PrPc can be used as reporter for binding of other proteins to PrPc by measuring changes in T1-NMR relaxation times of 9-aa upon PrP-protein complex formation. This assay is applied to probe the binding of two proteins reported to bind to PrPc under NMR conditions.
AD C. Mangels, A.O. Frank, J. Ziegler, K. Schweimer, W. Reindl, P. Rösch, S. Schwarzinger: Department of Biopolymers, University of Bayreuth, 95440 Bayreuth, Germany; R.S. Leliveld, R. Klingenstein, C. Korth: Institute of Neuropathology, Heinrich-Heine-University, 40225 Düsseldorf, Germany; D. Willbold: Institute for Physical Biology, Heinrich-Heine-University Düsseldorf, at the Research Centre Jülich, 52425 Jülich, Germany. E-mail: stephan.schwarzinger@uni-bayreuth.de
SP englisch
PO Italien