Hot spots in prion protein for pathogenic conversion.

ABSTRACT: Prion proteins are key molecules in transmissible spongiform encephalopathies (TSEs), but the precise mechanism of the conversion from the cellular form (PrP(C)) to the scrapie form (PrP(Sc)) is still unknown. Here we discovered a chemical chaperone to stabilize the PrP(C) conformation and identified the hot spots to stop the pathogenic conversion. We conducted in silico screening to find compounds that fitted into a "pocket" created by residues undergoing the conformational rearrangements between the native and the sparsely populated high-energy states (PrP*) and that directly bind to those residues. Forty-four selected compounds were tested in a TSE-infected cell culture model, among which one, 2-pyrrolidin-1-yl-N-[4-[4-(2-pyrrolidin-1-yl-acetylamino)-benzyl]-phenyl]-acetamide, termed GN

SUBMITTER: Kuwata K 

PROVIDER: S-EPMC1924567 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature