This title appears in the Scientific Report :
2009
Binding of TCA to the prion protein: mechanism, implication for therapy, and application as probe for complex formation of bio-macromolecules
Binding of TCA to the prion protein: mechanism, implication for therapy, and application as probe for complex formation of bio-macromolecules
Tricyclic aromatic compounds (TCA) are promising candidates for treatment of transmissible spongiform encephalopathies. Direct binding to the cellular prion protein (PrPC) has been proposed as anti-prion active mechanism. We here show by means of NMR-spectroscopy that binding of TCA occurs with mill...
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Personal Name(s): | Mangels, C. |
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Frank, A.O. / Ziegler, J. / Klingenstein, R. / Schweimer, K. / Willbold, D. / Korth, C. / Rösch, P. / Schwarzinger, S. | |
Contributing Institute: |
Strukturbiochemie; ISB-3 JARA - HPC; JARA-HPC |
Published in: | Journal of biomolecular structure & dynamics, 27 (2009) S. 163 - 170 |
Imprint: |
Guilderland, NY
Adenine Press
2009
|
Physical Description: |
163 - 170 |
Document Type: |
Journal Article |
Research Program: |
Funktion und Dysfunktion des Nervensystems |
Series Title: |
Journal of Biomolecular Structure & Dynamics
27 |
Subject (ZB): | |
Publikationsportal JuSER |
Tricyclic aromatic compounds (TCA) are promising candidates for treatment of transmissible spongiform encephalopathies. Direct binding to the cellular prion protein (PrPC) 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 PrPC. Because biologically inactive 9-aminoacridine (9-aa) binds with similar K-D as anti-prion active quinacrine, direct interaction with PrPC 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. |