NR ATNF
AU Wolff,M.; Santuccione,A.; Jansen,K.; Schachner,M.; Riesner,D.
TI PrP-Binding of Peptides selected by Phage Display as Therapeutical Approach
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Human prions, risk of blood products, and therapy HUMAN-03
PT Konferenz-Poster
AB Conversion of PrP from the alpha-helical conformation into the beta-sheet rich isoform is a central event in the course of prion diseases. Stabilization of the cellular isoform and inhibition of the conversion to the beta-sheet rich state may be a suitable approach for prevention or therapy of prion diseases. This stabilization can be achieved by PrP ligands binding specifically the cellular isoform. We identified more than hundred PrP-binding peptide sequences by phage display. From these the most promising 40 peptides were synthesized. Afterwards we examined their ability to inhibit conversion of PrP into the beta-sheet rich isoform in a SDS-based in vitro conversion system (Jansen K. et al., 2001). The influence on the structural transition was determined by circular dichroism spectroscopy and the potential to inhibit formation of aggregates was analyzed by differential ultracentrifugation. Finally we could identify one peptide that enhances PrP solubility at low SDS concentrations and is able to delay conversion into the beta-sheet rich isoform. Crosslinking of PrP and peptide suggests that it binds mainly to monomeric PrP and decreases formation of the PrP dimer. Thus stabilization of the cellular isoform of PrP by specifically binding peptides is possible and might be a therapeutical approach for prion diseases.
AD Michael Wolff, Katja Jansen, Detlev Riesner, Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Germany D-40225; Antonella Santuccione, Melitta Schachner, Zentrum für Molekulare Neurobiologie, Universität Hamburg, Germany D-29246
SP englisch
PO Deutschland