TY  - JOUR
AU  - Mangels, C.
AU  - Frank, A.O.
AU  - Ziegler, J.
AU  - Klingenstein, R.
AU  - Schweimer, K.
AU  - Willbold, D.
AU  - Korth, C.
AU  - Rösch, P.
AU  - Schwarzinger, S.
TI  - Binding of TCA to the prion protein: mechanism, implication for therapy, and application as probe for complex formation of bio-macromolecules
JO  - Journal of biomolecular structure & dynamics
VL  - 27
SN  - 0739-1102
CY  - Guilderland, NY
PB  - Adenine Press
M1  - PreJuSER-6512
SP  - 163 - 170
PY  - 2009
N1  - 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.
AB  - 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.
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000270000500006
UR  - https://juser.fz-juelich.de/record/6512
ER  -