Broad spectrum kinase binding agents
Provided herein are compounds that are broad-spectrum protein kinase binding agents, detectable tracers comprising such compounds, and method of use thereof for the detection of protein kinases.
1. A broad-spectrum kinase binding agent of formula:
2. The broad-spectrum kinase binding agent of claim 1 , comprising a non-natural abundance of one or more stable heavy isotopes.
3. A broad-spectrum kinase binding agent attached to a functional element or solid surface, comprising a moiety of formula:
attached to the functional element or solid surface.
4. The broad-spectrum kinase binding agent of claim 3 , wherein the solid surface is selected from a sedimental particle, a membrane, glass, a tube, a well, a self-assembled monolayer, a surface plasmon resonance chip, or a solid support with an electron conducting surface.
5. The broad-spectrum kinase binding agent of claim 4 , wherein the sedimental particle is a magnetic particle.
6. The broad-spectrum kinase binding agent of claim 3 , wherein the functional element is selected from a detectable element, an affinity element, and a capture element.
7. The broad-spectrum kinase binding agent of claim 6 , wherein the detectable element comprises a fluorophore, chromophore, radionuclide, electron opaque molecule, a MRI contrast agent, SPECT contrast agent, or mass tag.
8. The broad-spectrum kinase binding agent of claim 3 , wherein CC-1852 or CC-1861 is attached to the functional element directly or via a linker.
9. The broad-spectrum kinase binding agent of claim 8 , wherein the linker comprises —[(CH 2 ) 2 O] n —, wherein n is 1-20.
10. The broad-spectrum kinase binding agent of claim 9 , wherein the linker is attached to CC-1852 or CC-1861, and/or the functional element, by an amide bond.
11. The broad-spectrum kinase binding agent of claim 3 , comprising a structure of:
wherein X is a functional element or solid surface.
12. The broad-spectrum kinase binding agent of claim 11 , wherein X is a fluorophore.
13. The broad-spectrum kinase binding agent of claim 12 , comprising a structure of:
14. The broad-spectrum kinase binding agent of claim 3 , comprising a structure of:
wherein X is a functional element or solid surface.
15. The broad-spectrum kinase binding agent of claim 14 , wherein X is a fluorophore.
16. The broad-spectrum kinase binding agent of claim 15 , comprising a structure of:
17. A method of detecting or quantifying kinases in a sample, comprising contacting the sample with a composition of claim 3 and detecting or quantifying the functional element of a signal produced thereby.
18. A method of isolating kinases from a sample, comprising contacting the sample with a broad-spectrum kinase binding agent of claim 3 , and separating the functional element of the solid surface, as well as the bound kinases, from the unbound portion of the sample.
19. A method of characterizing the identities of the kinases in a sample comprising isolating the kinases from a sample by the method of claim 18 , and analyzing the isolated kinases by mass spectrometry.
20. A method of monitoring interactions between kinases and unmodified biomolecules comprising contacting the sample with a broad-spectrum kinase binding agent of claim 3 .