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Published on: September 8, 2016
Selective precipitation of prions by polyoxometalate complexes
In Su Lee1, Jeffrey R Long, Stanley B Prusiner
1Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Journal of the American Chemical Society
|October 6, 2005
Summary
Polyoxometalate anions can selectively precipitate infectious prion proteins (PrPSc) over normal ones (PrPC), enhancing diagnostic assays. Optimal selectivity was achieved with specific Keggin-type anions at higher concentrations than currently used.
Area of Science:
- Biochemistry
- Materials Science
- Analytical Chemistry
Background:
- Prion diseases are linked to the infectious isoform of the prion protein (PrPSc).
- Current diagnostic methods, like conformation-dependent immunoassays (CDI), face sensitivity limitations.
- Selective precipitation of PrPSc is a potential strategy to improve diagnostic sensitivity.
Purpose of the Study:
- To evaluate the efficacy of various polyoxometalate anions in selectively precipitating PrPSc over PrPC.
- To optimize the conditions for PrPSc precipitation to enhance CDI sensitivity.
- To elucidate the role of polyoxometalate structure and charge density in PrPSc precipitation.
Main Methods:
- Experiments were conducted using neutralized aqueous solutions containing different polyoxometalate anions.
- The selectivity of precipitation for PrPSc over PrPC was assessed.
- Solution structures were assigned using Nuclear Magnetic Resonance (NMR) and infrared spectroscopy.
Main Results:
- The Keggin-type anion Na2H[PW12O40] demonstrated optimal selectivity at a higher concentration (2.48% w/v) than the current CDI protocol (0.31% w/v).
- A trend in optimal concentrations was observed for Keggin anions, correlating with their charge density: [HBW11O39]8- < [SiW11O39]8- < [PW11O39]7- = [H2W12O40]6-.
- Larger polyoxometalate anions suppressed PrPSc precipitation in a concentration-dependent manner.
Conclusions:
- Specific polyoxometalate anions, particularly Keggin-type structures, can effectively and selectively precipitate PrPSc.
- The findings suggest a precipitation mechanism involving Keggin anions binding to PrPSc, potentially improving diagnostic assay sensitivity.
- Optimizing polyoxometalate type and concentration is crucial for enhancing PrPSc detection.
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