Assay for measuring binding affinity for cardiolipin of biologically active compounds
The present invention relates to a method for the evaluation of binding affinity of biologically active substances for cardiolipin based on acridinium salt utilization as a fluorescent probe.
1 . An assay method, comprising:
incubating a solution comprising a compound of interest, a lipid vesicle containing cardiolipin, and 3,6-di(azetidin-1-yl)-10-(3-(trimethylsilyl)propyl)acridin-10-ium iodide (I)
measuring fluorescence intensity at an excitation wavelength of 497 nm and at an emission wavelength of 529 nm, respectively.
2 . The method of claim 1 , wherein the compound of interest is an endogenous compound.
3 . The method of claim 1 , wherein the compound of interest comprises a metal cation.
4 . The method of claim 1 , wherein the compound of interest is an xenobiotic.
5 . The method of claim 1 , wherein the compound of interest comprises an ammonium or phosphonium cation.
6 . The method of claim 1 , wherein the compound of interest is an anthracycline or anthracenedione.
7 . The method of claim 1 , wherein the compound of interest is an aminoglycoside.
8 . The method of claim 1 , wherein the solution further comprises a buffer.
9 . The method of claim 1 , wherein 3,6-di(azetidin-1-yl)-10-(3-(trimethylsilyl)propyl)acridin-10-ium iodide is in a concentration of from 0.2 μM to 25 μM in the solution.
10 . The method of claim 1 , wherein the solution is incubated at 37° C.
11 . The method of claim 1 , further comprising determining an EC 50 value of the compound of interest after the measuring step.
12 . The method of claim 1 , wherein, before the incubating step, the method further comprises:
mixing the compound of interest and a lipid vesicle containing cardiolipin to form an intermediate solution;
incubating the intermediate solution; and
adding 3,6-di(azetidin-1-yl)-10-(3-(trimethylsilyl)propyl)acridin-10-ium iodide into the intermediate solution.
13 . A kit comprising:
3,6-di(azetidin-1-yl)-10-(3-(trimethylsilyl)propyl)acridin-10-ium iodide;
a buffer; and
a material containing cardiolipin.