Development and structural determination of an anti-PrP^C aptamer that blocks pathological conformational conversion of prion protein.

ABSTRACT: Prion diseases comprise a fatal neuropathy caused by the conversion of prion protein from a cellular (PrP^C) to a pathological (PrP^Sc) isoform. Previously, we obtained an RNA aptamer, r(GGAGGAGGAGGA) (R12), that folds into a unique G-quadruplex. The R12 homodimer binds to a PrP^C molecule, inhibiting PrP^C-to-PrP^Sc conversion. Here, we developed a new RNA aptamer, r(GGAGGAGGAGGAGGAGGAGGAGGA) (R24), where two R12s are tandemly connected. The 50% inhibitory concentration for the formation of PrP^Sc (IC₅₀) of R24 in scrapie-infected cell lines was ca. 100 nM, i.e., much lower than that of R12 by two orders. Except for some antibodies, R24 exhibited the lowest recorded IC₅₀ and the highest anti-prion activity.

SUBMITTER: Mashima T 

PROVIDER: S-EPMC7080826 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature