G - Physics – 01 – N
Patent
G - Physics
01
N
G01N 33/50 (2006.01) G01N 33/68 (2006.01) H01J 49/04 (2006.01)
Patent
CA 2387316
The present invention provides a method and apparatus for detecting the noncovalent binding of a potential ligand (such as a drug candidate) to a target molecule, e.g. a biochemical macromolecule such as a protein. The method is based on the Taylor dispersion of an initially sharp boundary between a carrier solution, and an analyte solution that contains the potential ligand(s) and the target molecule. Dispersion profiles of one or more potential ligands are monitored by mass spectrometry at the exit of the laminar flow tube. Potential ligands will usually be relatively small molecules that have large diffusion coefficients. In the absence of any noncovalent interactions in solution, very steep dispersion profiles are expected for these potential ligands. However, a ligand that binds to a large target molecule in solution, will show a diffusion coefficient that is significantly reduced, thus resulting in a less steep dispersion profile. Noncovalent binding can therefore be detected by monitoring dispersion profiles of potential ligands in the presence and in the absence of the target molecule. In contrast to other mass spectrometry-based methods for detecting noncovalent interactions, this method does not rely on the structural integrity of the complex in the gas phase. This method has an excellent sensitivity and selectivity, therefore it can be used for testing multiple potential ligands simultaneously. The method is therefore useful for the screening of compound libraries.
Clark Sonya M.
Konermann Lars
Clark Sonya M.
Konermann Lars
The University Of Western Ontario
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