Screening study of prion binding agents and their inhibitory effect on the conversion of prion protein

Abstract

Prion is a host-encoded protein and folds into at least two conformations, physiological PrPC and pathogenic PrPSc. PrPSc mediates the conversion of PrPC into PrPSc. Since prion-binding agents are expected to show inhibitory or stimulating effects on the conversion of prion protein, the binding compounds are promising candidates for the anti-prion disease agents. We established an ELISA assay system using the prion peptide PrP(106-126) and an anti-prion monoclonal antibody 3174 to detect the prion-binding activity, and tested the activity of the extracts of medical plants and microbial culture broth samples. Some of the samples that showedprion-binding activity in this ELISA assay were advanced to the next assay todetect the inhibition on conversion of PrPC into PrPSc using ScN2a cells. Finally we found that some compounds derived from chlorophylls showed clear inhibition for the prion protein conversion. The mechanism ofinhibition by these chemicals may stand on the binding to the 3174 epitope area of prion protein and interrupting the PrPC-PrPSc interaction. The safety of these chemicals are so sufficient, since they have already used as food additives (coloring agents). Furthermore, one of, them, sodium copper chlorophyllin, has managed as a drug to cure bad breath. They are expected to be good lead compounds to develop the new anti-prion drugs.