Abstract: The present disclosure relates to methods and compositions for the detection of infectious proteins or prions in samples, including the diagnosis of prion related diseases. One embodiment is an ultrasensitive method for detecting PrP-res (PrPSc) that allows the use of recombinant PrP-sen (rPrP-sen) as a substrate for seeded polymerization. A sample is mixed with purified rPrP-sen to make a reaction mix which is incubated to permit aggregation of the rPrP-sen with the PrP-res that may be present in the sample. Any aggregates are intermittently disaggregated by agitation (for example by sonication) and the reaction allowed to proceed to amplify target substrate. Any rPrP-res(Sc) in the reaction mix is detected to indicate the presence of PrP-res in the original sample. This assay, which is called rPrP-PMCA, is surprisingly much faster than existing PMCA methods, yet it still retains sufficient sensitivity to detect extremely low levels of PrP-res.

Abstract: Peptides are disclosed that inhibit the conversion of protease sensitive prion protein (PrPsen) to the protease resistant isoform (PrPres). These peptides comprise discrete fragments of prion proteins, and are shown to inhibit the in vitro conversion of PrPsen to PrPres in a cell-free system. Numerous peptides are disclosed that include at least two amino acid residues from the highly amyloidogenic region P113-120 of the PrP protein. None of these peptides conferred protease-resistance to the PrPsen molecules. The presence of residues 119 and 120 from the highly hydrophobic sequence AGAAAAGA (position 113 to 120) produced a particular inhibitory effect. The inhibition occurred with a high degree of specificity (e.g. with an IC50 of less than about 1000 &mgr;M).

Abstract: Peptides are disclosed that inhibit the conversion of protease sensitive prion protein (PrPsen) to the protease resistant isoform (PrPres). These peptides comprise discrete fragments of prion proteins, and are shown to inhibit the in vitro conversion of PrPsen to PrPres in a cell-free system. Numerous peptides are disclosed that include at least two amino acid residues from the highly amyloidogenic region P113-120 of the PrP protein. None of these peptides conferred protease-resistance to the PrPsen molecules. The presence of residues 119 and 120 from the highly hydrophobic sequence AGAAAAGA (position 113 to 120) produced a particular inhibitory effect. The inhibition occurred with a high degree of specificity (e.g. with an IC50 of less than about 1000 &mgr;M).

Abstract: Peptides are disclosed that inhibit the conversion of protease sensitive prion protein (PrPsen) to the protease resistant isoform (PrPres). These peptides comprise discrete fragments of prion proteins, and are shown to inhibit the in vitro conversion of PrPsen to PrPres in a cell-free system. Numerous peptides are disclosed that include at least two amino acid residues from the highly amyloidogenic region P113-120 of the PrP protein. None of these peptides conferred protease-resistance to the PrPsen molecules. The presence of residues 119 and 120 from the highly hydrophobic sequence AGAAAAGA (position 113 to 120) produced a particular inhibitory effect. The inhibition occurred with a high degree of specificity (e.g. with an IC50 of less than about 1000 &mgr;M).