Structural Conversion Rate Changes of Recombinant Bovine Prion by Designed Synthetic Peptides

An understanding of structural changes and self-assembly of proteins, which are thought to involve specific peptide–peptide interactions, will contribute to the development of therapeutic agents and diagnosis for the detection of conformational diseases. We hypothesize that certain peptides may contribute to the conformational change of prion proteins. The present paper describes the discovery of prion-related synthetic peptides which influence structural conversion of recombinant bovine prion protein. The peptides designed are prion-protein fragments containing core domains consisting of α-helical (human prion protein fragment 180–195) and known β-sheet (human prion protein fragment 169–175) structures. Additionally several reported known β-sheet breaker peptides and a conjugate consisting of β-sheet and α-helix segments based on the secondary structures of human prion protein, designated HPPSH, have been chemically synthesized by the conventional Fmoc solid-phase method and characterized by circular dichroism and the Thioflavin T fluorescence method. Our data indicated that the co-existence of peptides, HPPSH or other prion fragment peptides involving toxic core sequence (the fragment 106–126), influenced the kinetic rate of aggregation and the lag-time of fibril formation of recombinant bovine prion protein except the core sequence itself. The method will be used for discovery of responsible material from natural resources. And designed peptides can be also used for bio-detection.