NR AUSW
AU Kehler,C.; Gilch,S.; Schätzl,H.M.
TI Peptide aptamers: a novel anti-prion approach
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Therapie THE-02
PT Konferenz-Poster
AB
The prophylactic and therapeutic regimens against prion diseases are limited. Several classes of molecules have been characterized, including e. g. chemical compounds, inhibitors of signalling molecules, beta sheet breaker peptides or modified prion proteins. Only a few have an effect on the progression of prion disease when administered to infected animals.
We recently found RNA aptamers to inhibit accumulation of high molecular weight PrPsc aggregates in prion-infected cells. Due to the limitations of these molecules, we extended our experimental strategies and decided to select peptide aptamers binding to PrPc. We constructed a constrained peptide library presented on the actice-site loop of the E. coli thioredoxin A (trx A) protein. In a yeast-two-hybrid screen employing full-length murine PrP (aa 23-231) as a bait we fished several peptides which reproducibly bind to PrPc. For expression in eukaryotic cells, these molecules are fused to N- and C-terminal signal peptides for entry of the secretory pathway and addition of a GPI-anchor, respectively. First studies show that trx A is targeted to the plasma membrane upon this manipulations. Further experiments will show whether the selected peptide aptamers are able to interfere with prion propagation in prion infected cells.
AD Claudia Kehler, Sabine Gilch, Hermann M. Schätzl, Institute of Virology, Prion Research Group, Trogerstr. 30, 81675 Munich, Germany
SP englisch
PO Deutschland
OR Tagungsband