Preference toward a polylysine enantiomer in inhibiting prions

Abstract

Differential anti-prion activity of polylysine enantiomers was studied. Based on our recent discovery that poly-l-lysine (PLK) is a potent anti-prion agent, we investigated suppression of prions in cultured cells using poly-d-lysine (PDK). The results showed that PDK was more efficacious than PLK to inhibit prions. Protein misfolding cyclic amplification assay demonstrated improved efficacy of PDK in inhibiting plasminogen-mediated prion propagation, corresponding to the enantio-preference of PDK observed in cultured cells. Furthermore, our study demonstrated that polylysines formed a complex with plasminogen. These results propose to hypothesize a plausible mechanism that elicits prion inhibition by polylysine enantiomers.