Polypeptides derived from vitamin d nuclear receptor, and...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 14/705 (2006.01) A61K 38/17 (2006.01) A61P 3/14 (2006.01) A61P 33/14 (2006.01) A61P 35/00 (2006.01) C12N 15/10 (2006.01) C12N 15/12 (2006.01) C12N 15/63 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2390898

The invention concerns polypeptides derived from vitamin D nuclear receptor, said nuclear receptor comprising a ligand-binding domain, or LBD, said LBD containing a flexible insertion domain. Said polypeptides are characterised in that the LBD flexible insertion domain is modified by substituting or suppressing at least 30 acids. The invention also concerns the use of said polypeptides in particular for screening synthetic vitamin D analogues or for producing tests (double or triple hybrid) for identifying other proteins (activator, repressor,...) interacting with the vitamin D receptor using constructs containing the polypeptide fused with Ga14 for example, or for analysing three-dimensional structures of complexes formed between said polypeptides and a particular molecule by crystallography or NMR.

L'invention a pour objet des polypeptides dérivés du récepteur nucléaire de la vitamine D, ledit récepteur nucléaire comprenant un domaine de liaison au ligand, ou LBD, ce LBD contenant un domaine d'insertion flexible, lesdits polypeptides dérivés étant caractérisés en ce que le domaine d'insertion flexible du LBD est modifié par substitution ou suppression d'au moins environ 30 acides, ainsi que l'utilisation de ces polypeptides notamment dans le cadre du criblage d'analogues synthétiques de la vitamine D, ou dans la mise au point de tests (double ou triple hybride) pour l'identification d'autres protéines (activateur, répresseur,...) interagissant avec le récepteur de la vitamine D par l'utilisation de constructions contenant le polypeptide en fusion avec Gal4 par exemple, ou dans le cadre de l'analyse de la structure tridimensionnelle des complexes formés entre ces polypeptides et une molécule particulière par cristallographie ou RMN.

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