Patent ID: 7413906

Claim:
A method of detecting a disease characterized by protein misfolding, the method comprising: (a) providing a test protein suspected of being misfolded; (b) contacting the protein with an exchange buffer comprising a denaturant and deuterium, the exchange buffer having a denaturant concentration; (c) contacting the test protein with a mass spectrometry matrix medium; (d) determining a change in mass of the test protein resulting from hydrogen-deuterium exchange by mass spectrometry; (e) varying the denaturant concentration of the exchange buffer; (f) repeating steps (a)-(e) a desired number of times to generate a denaturation curve of the tested protein; and (g) analyzing the change in mass of the test protein as a function of the denaturant concentration to determine a stability of the test protein; and (h) comparing the stability of the test protein suspected of being misfolded with a known stability of a properly folded test protein, wherein a change in stability of the test protein when compared with the known stability of the properly folded test protein is indicative of a disease characterized by protein misfolding.