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Burlingame, CA, United States

Described herein are methods useful for screening candidate biochemical entities targeting a target biochemical entity and methods useful for identifying a binding moiety for a target biochemical entity. The invention provides methods of screening drug candidates targeting a target biomolecule, comprising selecting a drug candidate based on a signal difference between a first signal and a second signal. The signal difference indicates a difference in an in vivo or in vitro pharmacological property. The first signal is produced upon binding between the target biomolecule and a first candidate by contacting the target biomolecule with the first candidate, and the second signal is produced upon binding between the target biomolecule and a second candidate by contacting the target biomolecule with the second candidate.


A system for making molecules, and proteins in particular, suitable for detection by a surface-selective nonlinear optical technique. A first use of the invention is for determining a proteins structure in real space and real time. A second use of the invention is to detect a protein or its activity (conformational change). A third use of the invention is for drug screening. A further aspect of the present invention is measuring probe tilt angle orientation in an oriented protein.


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.


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.


Patent
Biodesy LLC | Date: 2013-04-25

The present invention discloses, inter alia, methods for labeling a target protein with an SHG-active probe for detection by second harmonic or sum-frequency generation in order to identify agents which bind to an allosteric site on the target protein thereby altering its structural conformation

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