A tetracationic porphyrin with dual anti-prion activity.

ABSTRACT: Prions are deadly infectious agents made of PrP^Sc, a misfolded variant of the cellular prion protein (PrP^C) which self-propagates by inducing misfolding of native PrP^C. PrP^Sc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrP^C, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrP^C fold, hindering conversion to PrP^Sc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrP^C

SUBMITTER: Masone A 

PROVIDER: S-EPMC10448035 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature