Method for the identification and characterization of...

G - Physics – 01 – N

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G01N 33/74 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2286761

The present invention is directed to a methodology to study the effect of ligands that can modulate functions of nuclear receptors, and specifically, their interaction with specific DNA or other transcription factors. These receptors play a major role in the cascade of inter and intracellular physiological and biochemical events. They generally have a modular construction which enables them to recognize and bind to certain DNA sequences, or binding elements, such as hormone response elements. Various ligands, such as hormones, affect this interaction. In accordance with the methodology presented herein, measurements of such interactions are taken in real time and kinetic pattern. This allows the user to identify and to characterize ligands that are able to affect a receptor's interaction with its binding element. Hence, the present invention provides a useful tool for the elucidation, and development of ligands that affect transcription of target genes, either directly or indirectly.

L'invention concerne une méthodologie qui permet d'étudier l'effet de ligands pouvant moduler les fonctions des récepteurs nucléaires, notamment leur interaction avec un ADN spécifique ou d'autres facteurs de transcription. Ces récepteurs jouent un rôle majeur dans la cascade des phénomènes physiologiques et biochimiques intercellulaires et intracellulaires. Ils ont généralement une structure modulaire, qui leur permet de reconnaître certaines séquences d'ADN ou éléments de liaison, tels que des éléments de réponse hormonale, et de s'y fixer. Divers ligands, tels que les hormones, affectent cette interaction. Selon la méthodologie présentée ici, les mesures de ces interactions sont effectuées en temps réel et concernent leur cinétique, ce qui permet à l'utilisateur d'identifier et de caractériser les ligands capables d'affecter l'interaction d'un récepteur avec son élément de liaison. La présente invention constitue donc un outil utile pour élucider et développer des ligands affectant, directement ou indirectement, la transcription de gènes cibles.

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