The depletion of α and β PrP from complex mixtures

Prion disorders occur when endogenous prion protein (PrPC) undergoes a conformational change from a predominantly α-helix-rich structure to an insoluble β-sheet-rich structure (PrPSc). The resulting PrPSc then in some way facilitates the progressive transformation of nearby PrPC to PrPSc. In time this results in the deposition of insoluble PrPSc aggregates in the brain; aggregate deposition is irreversible and is ultimately fatal. Prion diseases are transmissible orally or through transplantation (including blood transfusion). Current diagnostic methods are limited in that they lack the ability to distinguish qualitatively between PrPC and PrPSc. PrP has been shown to bind divalent cations including copper and zinc, these cations are toxic and thus of limited use in the removal of PrP from solutions destined for administration to subjects. We have immobilised Fe3+ to an inert Sepharose resin; this resin was capable of quantitatively removing endogenous and recombinant PrPC and recombinant β PrP from complex solutions. The low toxicity of Fe3+ suggests that the resin described in this report may be of practical use in the depletion of PrP from blood products destined for human use.