Crystals and structural coordinate of protein complex and...

C - Chemistry – Metallurgy – 07 – K

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C07K 19/00 (2006.01) C07B 61/00 (2006.01) C07K 14/535 (2006.01) C07K 14/715 (2006.01) G01N 33/15 (2006.01) G01N 33/68 (2006.01) G06F 17/30 (2006.01) G06F 17/50 (2006.01)

Patent

CA 2363961

Crystals of a protein complex composed of granulocyte colony-stimulating factor (G-CSF) and the G-CSF binding moiety of a G-CSF receptor; and the structural coordinate of each atom determined by the crystal structure analysis procedure from these crystals. By using this structural coordinate, it is possible to identify, search, evaluate or design a G-CSF mutant which has a biological activity higher than G-CSF occurring in nature or an inhibitory activity on G-CSF and is derived by substitution, deletion, insertion or chemical modification of one or more amino acid residues, an agonist which is a compound having a biological activity comparable or superior to the biological activity of G-CSF, and an antagonist which is a compound inhibiting the biological activity of G-CSF.

L'invention concerne des cristaux constitués d'un complexe protéique qui comprend le facteur stimulant les colonies de granulocytes (G-CSF) et le fragment d'un récepteur de G-CSF fixant ce dernier; ainsi que les coordonnées structurales de chaque atome déterminées par l'analyse de la structure cristalline desdits cristaux. Ces coordonnées permettent d'identifier, de rechercher, d'évaluer et de générer un mutant de G-CSF qui possède une activité biologique supérieure au G-CSF naturel ou une activité inhibitrice du G-CSF et qui est dérivé par substitution, délétion, insertion ou modification chimique d'un ou de plusieurs résidus d'acides aminés; un agoniste qui est un composé possédant une activité biologique comparable ou supérieure à celle du G-CSF; et un antagoniste qui est un composé inhibant l'activité biologique du G-CSF.

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