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Title: Methods to differentiate protein conformers

item Onisko, Bruce
item Silva, Christopher - Chris
item Carter, John

Submitted to: Patent Application
Publication Type: Patent Application
Publication Acceptance Date: 5/21/2013
Publication Date: 5/21/2013
Citation: Onisko, B.C., Silva, C.J., Requena, J.R., Carter, J.M. 2013. Methods to differentiate protein conformers. Patent Application. US Patent 8,445,642.

Interpretive Summary:

Technical Abstract: Discrimination and quantitation of protein conformers is an unsolved scientific problem. Many proteins are known to exist in two or more conformations (e.g. PrPc and PrPsc in CJD, CWD, BSE, TME, scrapies; sup35 and ure2p in yeast; CPEB in long term memory formation; huntington and A-beta in neurological disease), and these conformers have significantly different biological properties. Discrimination and quantitation of these conformers is essential for diagnosing subclinical disease in animals and for monitoring the presence of disease-forming protein contamination of body fluids (e.g. blood, urine, saliva) or environmental samples. Proteins that exist in two or more conformers can be differentiated by their unique reactivities toward bifunctional crosslinking reagents (e.g. homo, hetero, or “zero length” reagents). Since distances between specific amino acid residues in the two conformers will be different, a suitably chosen crosslinking reagent will react with one but not the other conformer (and vice versa).