Methods for measuring protein kinase and phosphatase activity

C - Chemistry – Metallurgy – 12 – Q

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C12Q 1/42 (2006.01) C12Q 1/48 (2006.01) G01N 33/50 (2006.01)

Patent

CA 2484397

The invention provides fluorescence-based assays for determining the phosphorylating or the dephosphorylating activity of an enzyme acting on a substrate molecule. The substrate comprises at least one moiety that is capable of being phosphorylated or dephosphorylated by an enzyme to yield a product, the substrate being labelled with a fluorescent dye, and which is capable of exhibiting change in fluorescence intensity and fluorescence lifetime upon phosphorylation of the dye-labelled substrate or upon dephosphorylation of the dye-labelled phosphorylated substrate. In preferred embodiments, the substrate is labelled with a fluorescent dye selected from the acridone and the quinacridone classes of dyes. Also provided is a method for screening for a test agent whose effect on the phosphorylating or dephosphorylating activity of an enzyme is to be determined.

Cette invention porte sur des analyses par fluorescence servant à déterminer l'activité phosphorylante ou déphosphorylante d'une enzyme agissant sur une molécule substrat. Le substrat comprend au moins une fraction pouvant être phosphorylée ou déphosphorylée par une enzyme afin qu'on obtienne un produit, lequel substrat est marqué par un fluorochrome, et pouvant présenter une variation de l'intensité de la fluorescence et de la durée de vie de la fluorescence sous l'effet de la phosphorylation du substrat marqué par un colorant ou de la déphosphorylation du substrat phosphorylé marqué par un colorant. Dans des modes de réalisation préférés de cette invention, le substrat est marqué par un fluorochrome sélectionné parmi les classes de colorants acridone et quinacridone. Cette invention concerne également un procédé de criblage d'un agent d'essai dont l'effet sur l'activité phosphorylante ou déphosphorylante d'une enzyme doit être déterminée.

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