3d structure of polypeptides containing a tpr-structure...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/12 (2006.01) A61K 38/17 (2006.01) C07K 14/47 (2006.01) G01N 33/50 (2006.01) G06F 17/50 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2404658

The invention relates to 3-D structures of a polypeptide, whereby, in the 3-D structure, the polypeptide contains at least one amino acid sequence of a TPR- structure motif from a Hop protein, or a derivative thereof. The invention further relates to crystals, comprising at least one polypeptide in their asymmetric unit and, optionally, at least one further compound, whereby the polypeptide adopts the above 3D-structure in the crystal. Furthermore, methods for the production of such crystals and compounds, having the property of binding, as ligands, to structural regions of a Hop protein are disclosed. Additionally, a method for the identification of inhibitors is disclosed, whereby ligands with inhibitor functions for the interaction of a Hop protein with at least one chaperone protein are obtained. Such inhibitors are useful for the treatment of tumour disease states, immunosupression, GVDH, or the treatment of viral infections.

L'invention concerne des formes spatiales d'un polypeptide, ledit polypeptide contenant au moins un séquence d'aminoacide d'un motif de structure TPR d'une protéine de houblon ou un dérivé d'un séquence d'aminoacide de ce type. L'invention concerne en outre des cristaux qui contiennent dans leur unité asymétrique, au moins un polypeptide ou éventuellement au moins un autre composé. Dans le cristal, les polypeptides adoptent la forme spatiale décrite ci-dessus. L'invention concerne par ailleurs des procédés permettant de préparer des cristaux et des composés de ce type, qui présentent comme propriété, le fait de se fixer, en tant que ligands, sur des zones structurales d'une protéine de houblon. Afin d'obtenir des ligands à fonction inhibitrice pour l'interaction entre une protéine de houblon et au moins une protéine de Chaperon, il est en outre prévu des procédés permettant d'identifier des inhibiteurs de ce type. Ces inhibiteurs peuvent s'utiliser comme médicaments et par exemple pour traiter des affections tumorales, l'immunodépression, les réactions du greffon contre l'hôte ou pour traiter des infections virales.

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