12 research outputs found
Mouse Prion Protein (PrP) Segment 100 to 104 Regulates Conversion of PrPC to PrPSc in Prion-Infected Neuroblastoma Cells
Rapid detection of malto-oligosaccharide-forming bacterial amylases by high performance anion-exchange chromatography
Rational Designed Polymer as a Metal-Free Catalyst for Hydroxylation of Benzene to Phenol with Dioxygen
Biosynthesis of the carbohydrate moieties of arabinogalactan proteins by membrane-bound ÎČ-glucuronosyltransferases from radish primary roots
A polymer-anchored cobalt(II) complex as a reusable catalyst for oxidation of benzene, ethylbenzene and cyclohexane
Highly efficient multi-metal catalysts for carbon dioxide reduction prepared from atomically sequenced metal organic frameworks
Enhanced oxidation power in photoelectrocatalysis based on a micrometer-localized positive potential in a terrace hetero pân junction
Floral nectar chemical composition of floral nectar in conventional and transgenic sweet orange, Citrus sinensis (L.) Osbeck, expressing an antibacterial peptide
An exo-ÎČ-(1â3)-d-galactanase from Streptomyces sp. provides insights into type II arabinogalactan structure
Influence of surface functionality of poly(propylene imine) dendrimers on protease resistance and propagation of the scrapie prion protein
Accumulation of PrP(Sc), an insoluble and protease-resistant pathogenic isoform of the cellular prion protein (PrP(C)), is a hallmark in prion diseases. Branched polyamines, including PPI (poly(propylene imine)) dendrimers, are able to remove protease resistant PrP(Sc) and abolish infectivity, offering possible applications for therapy. These dendrimer types are thought to act through their positively charged amino surface groups. In the present study, the molecular basis of the antiprion activity of dendrimers was further investigated, employing modified PPI dendrimers in which the positively charged amino surface groups were substituted with neutral carbohydrate units of maltose (mPPI) or maltotriose (m3PPI). Modification of surface groups greatly reduced the toxicity associated with unmodified PPI but did not abolish its antiprion activity, suggesting that the presence of cationic surface groups is not essential for dendrimer action. PPI and mPPI dendrimers of generation 5 were equally effective in reducing levels of protease-resistant PrP(Sc) (PrP(res)) in a dose- and time-dependent manner in ScN2a cells and in pre-existing aggregates in homogenates from infected brain. Solubility assays revealed that total levels of PrP(Sc) in scrapie-infected mouse neuroblastoma (ScN2a) cells were reduced by mPPI. Coupled with the known ability of polyamino dendrimers to render protease-resistant PrP(Sc) in pre-existing aggregates of PrP(Sc) susceptible to proteolysis, these findings strongly suggest that within infected cells dendrimers reduce total amounts of PrP(Sc) by mediating its denaturation and subsequent elimination