Methods using a nonlinear optical technique for detection of interactions involving a conformational change
AssigneeBiodesy, Inc.
InventorJoshua S. Salafsky
Life of this patent
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Abstract
A nonlinear optical technique, such as second or third harmonic or sum or difference frequency generation, is used to detect binding interactions, or the degree or extent of binding, that comprise conformational change. In one aspect of the present invention, the nonlinear optical technique detects a conformational change in a probe due to target binding. In another aspect of the invention, the nonlinear optical technique screens candidate probes by detecting a conformational change due to a probe-target interaction. In another aspect of the invention, the nonlinear optical technique screens candidate modulators of a probe-target interaction by detecting a conformational change in the presence of the modulator.
Claims46
1-20. (canceled)
A method for detecting a conformational change upon binding of a test molecule to a candidate binding partner in a sample comprising (a) contacting the test molecule with the candidate binding partner;
- (b) illuminating the contacted test molecule with a light beam at a fundamental frequency;
- (c) detecting the conformational change by measuring a physical property of a second-harmonic or sum-frequency light beam emanating from the sample.
A method for detecting a shift in average label angle of 5 degrees or less in a nonlinear-active label upon binding of the test molecule to a candidate binding partner in a sample comprising (a) contacting the test molecule with the candidate binding partner;
- (b) illuminating the contacted test molecule with a light beam at a fundamental frequency;
- (c) detecting the shift by measuring a physical property of a second-harmonic or sum-frequency light beam emanating from the sample.
A method for screening a candidate conformation blocker of a test molecule comprising (a) contacting the test molecule with a known binding partner and a candidate conformation blocker, wherein the test molecule undergoes a conformational change upon the binding with the known binding partner;
- (b) illuminating the contacted test molecule with a light beam at a fundamental frequency;
- (c) detecting the conformational change by measuring a physical property of a second-harmonic or sum-frequency light beam emanating from the sample.
A method for screening different types of binding partners of a test molecule in a sample comprising (a) contacting the test molecule with the binding partners;
- (b) illuminating the contacted test molecule with a light beam at a fundamental frequency;
- (c) measuring a physical property of a second-harmonic or sum-frequency light beam emanating from the sample;
- (d) determining the degree or extent of the binding between the test molecule and the binding partners based on the value of the physical property measured in step (c) thereby distinguishing different types of binding partners, wherein at least one of the binding partners induces a conformational change upon binding of a test molecule.
Dependencies are inferred from the claim text.