A method for high throughput thermodynamic screening of ligands

G - Physics – 01 – N

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G01N 33/53 (2006.01) G01N 33/557 (2006.01) G01N 33/566 (2006.01)

Patent

CA 2393422

The present invention provides a method of rapidly screening ligands on the basis of their binding affinity and binding enthalpy by carrying out binding assays at a minimum of two temperatures. This technique permits the selection for further optimization of lead ligands that bind to the target molecules with favorable enthalpies. Those ligands will exhibit higher solubilities in aqueous solution than ligands selected by conventional means, and may exhibit lower susceptibilities to resistant mutations. The method may be utilized as a standalone technique, or may be adapted to, for example, known high throughput screening technologies. The present invention further comprises an apparatus for carrying out the described methods.

La présente invention concerne une méthode permettant de réaliser un criblage rapide de ligands à partir de leur affinité de liaison et enthalpie de liaison, en effectuant des analyses de liaison à un minimum de deux températures. Cette technique permet de sélectionner, en vue d'une plus grande optimisation, des ligands potentiels se fixant à des molécules cibles avec des enthalpies favorables. Ces ligands présentent une plus grande solubilité dans une solution aqueuse que les ligands sélectionnés par des moyens conventionnels, et peuvent être moins sensibles aux mutations résistantes. Cette méthode peut être utilisée comme technique autonome, ou peut être adaptée, par exemple, à des technologies connues de criblage a haut rendement. La présente invention concerne également un appareil permettant de mettre en oeuvre ces méthodes.

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