Antimalarial Drug Quinacrine Binds to C-Terminal Helix of Cellular Prion Protein
- 11 July 2003
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 46 (17) , 3563-3564
- https://doi.org/10.1021/jm034093h
Abstract
Using NMR spectroscopy we show that the cellular prion protein constitutes a target for binding of various acridine and phenothiazine derivatives. We unambiguously map the quinacrine binding site of recombinant human prion protein to residues Tyr225, Tyr226, and Gln227 of helix α3, which is located near the “protein X” epitope. The millimolar dissociation constant of the complex suggests that in vivo inhibition of prion propagation occurs after 10000-fold concentration of quinacrine within endolysosomes.Keywords
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