Analysis of intracellular modifications

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/68 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2571730

Improved methods of determining the intracellular state of a protein as well as modifications of the protein are provided by introducing a surrogate fusion protein comprising a member of an enzyme fragment complementation complex and a target protein. After exposing cells transformed with the surrogate fusion protein to a change in environment, e.g. a candidate drug, the cells are lysed, the lysate separated into fractions or bands, conveniently by gel electrophoresis and transferring the proteins by Western blot to a membrane. The bands on the membrane are developed using the other member of the enzyme fragment complementation complex and a substrate providing a detectable signal. The method is found to provide high sensitivity and the ability to observe modifications of the target protein.

L'invention concerne des méthodes améliorées de détermination de l'état intracellulaire d'une protéine ainsi que de modifications de la protéine par introduction d'une protéine de fusion de substitution comprenant un élément d'un complexe de complémentation de fragments enzymatiques et une protéine cible. Après exposition des cellules transformées à l'aide d'une protéine de fusion de substitution à un changement d'environnement, par exemple, un médicament candidat, les cellules sont lysées, le lysat séparé en fractions ou bandes, de manière pratique par électrophorèse en gel et après transfert des protéines par transfert de type western sur une membrane. Les bandes sur la membrane sont développées à l'aide de l'autre élément du complexe de complémentation de fragments enzymatiques et d'un substrat fournissant un signal détectable. La méthode s'avère conférer une sensibilité élevée et la capacité à observer des modifications de la protéine cible.

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