Influence of Surface Groups on Poly(propylene imine) Dendrimers Antiprion Activity

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Title: Influence of Surface Groups on Poly(propylene imine) Dendrimers Antiprion Activity
Authors: McCarthy, James M.
Moreno, Beatriz Rasines
Filippini, Damien
Komber, Hartmut
Maly, Marek
Cernescu, Michaela
Brutschy, Bernhard
Appelhans, Dietmar
Rogers, Mark S.
Permanent link: http://hdl.handle.net/10197/4251
Date: 12-Dec-2012
Abstract: Prion diseases are characterized by the accumulation of PrP(Sc), an aberrantly folded isoform of the host protein PrP(C). Specific forms of synthetic molecules known as dendrimers are able to eliminate protease-resistant PrP(Sc) in both an intracellular and in vitro setting. The properties of a dendrimer which govern this ability are unknown. We addressed the issue by comparing the in vitro antiprion ability of numerous modified poly(propylene-imine) dendrimers, which varied in size, structure, charge, and surface group composition. Several of the modified dendrimers, including an anionic glycodendrimer, reduced the level of protease resistant PrP(Sc) in a prion strain-dependent manner. This led to the formulation of a new working model for dendrimer/prion interactions which proposes dendrimers eliminate PrP(Sc) by destabilizing the protein and rendering it susceptible to proteolysis. This ability is not dependent on any particular charge of dendrimer, but does require a high density of reactive surface groups.
Type of material: Journal Article
Publisher: American Chemical Society
Copyright (published version): 2012, American Chemical Society
Keywords: Dendrimers;PrPSc;Prions
DOI: 10.1021/bm301165u
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biology & Environmental Science Research Collection

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