4 research outputs found
Library based identification and characterisation of polymers with nano-FTIR and IR-sSNOM imaging
Influence of Surface Groups on Poly(propylene imine) Dendrimers Antiprion Activity
Prion diseases are characterized by the accumulation
of PrP<sup>Sc</sup>, an aberrantly folded isoform of the host protein
PrP<sup>C</sup>. Specific forms of synthetic molecules known as dendrimers
are able to eliminate protease-resistant PrP<sup>Sc</sup> 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<sup>Sc</sup> 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<sup>Sc</sup> 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
Influence of Surface Groups on Poly(propylene imine) Dendrimers Antiprion Activity
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