%0 Journal Article
%A Mangels, C.
%A Frank, A.O.
%A Ziegler, J.
%A Klingenstein, R.
%A Schweimer, K.
%A Willbold, D.
%A Korth, C.
%A Rösch, P.
%A Schwarzinger, S.
%T Binding of TCA to the prion protein: mechanism, implication for therapy, and application as probe for complex formation of bio-macromolecules
%J Journal of biomolecular structure & dynamics
%V 27
%@ 0739-1102
%C Guilderland, NY
%I Adenine Press
%M PreJuSER-6512
%P 163 - 170
%D 2009
%Z We thank Dr. Vilma Martins for providing a plasmid with the human PRNP-gene. Financial support from the Bavarian Prion Research Platform (ForPrion) and the Volkswagen-Stiftung (1/79968) is gratefully acknowledged.
%X 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.
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000270000500006
%U https://juser.fz-juelich.de/record/6512