Screening study of prion binding agents and their inhibitory effect on the conversion of prion
protein
Naoko Iwanami, Ushio Sankawa, Takaomi C. Saido, Yoshio Yamakawa, Masahiro Nishijima and Kiyotoshi Kaneko
National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502 Japan
<e-mail> nami@ncnp.go.jp
Abstract
Prion is a host-encoded protein and folds into at least two conformations, physiological PrP^ and pathogenic PrP^^ PrP^^ mediates the conversion of PrP^ into PrP^^. Since prion-binding agents are expected to show in- hibitory 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 3F4 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 showed prion-binding activity in this ELISA assay were advanced to the next assay to detect the inhibition on conversion of PrP^ into PrP^^ using ScN2a cells. Finally we found that some compounds derived from chlorophylls showed clear inhibition for the prion protein conversion.
The mechanism of inhibition by these chemicals may stand on the binding to the 3F4 epitope area of prion protein and interrupting the PrP^-PrP^^ in- teraction. 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.
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