Skip to Main Content

New kinase detection method helps identify targets for developing cancer drugs

Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

tao-a171.jpg
Purdue University professor Andy Tao developed a new kinase detection method that helps identify targets for developing cancer drugs. (Purdue Agricultural Communications/Tom Campbell).

Kinases are proteins that catalyze the transfer of a phosphate group to another protein, a process called phosphorylation that is key to a protein’s function. Many phosphorylated proteins are oncogenes, ones that can trigger the formation of cancer cells.

There are dozens of kinase inhibitors on the market used to treat cancer. But cancer cells adapt, making some drugs less effective. New kinase targets would lead to new drugs that could diversify treatment options for patients with hard-to-treat cancers, a long and tedious process.

“These are the critical molecules for cancer growth and proliferation,” said W. Andy Tao, Purdue professor of biochemistry and the senior author of the findings published in the journal ACS Central Science. “It’s important to know all the alternative kinases that can phosphorylate an oncogene, so if we see resistance, we re-target it.”

Previously there was no existing method available to systematically identify kinases responsible for phosphorylating an oncogene. Tao and collaborators from Purdue’s Department of Medicinal Chemistry and Molecular Pharmacology (MCMP), Department of Chemistry, and the Purdue Center for Cancer Research developed a powerful method that can rapidly screen for kinase-protein interactions. Tao and his collaborator, Chang-Deng Hu, professor of MCMP, met and devised the idea during a scientific retreat, but it took them several years to finally work out the technical details.

changdeng-h171.jpg
Purdue University professor Chang-Deng Hu collaborated on research that led to a new kinase detection method for developing cancer drugs. (Photo submitted by Chang-Deng Hu).

The method utilizes a known imaging assay called bimolecular fluorescence complementation (BiFC) in which a fluorescent protein is split into two pieces, labeled terminals N and C. One terminal is added to a suite of kinases, and the other is placed with a target oncogene.

“If the two proteins interact with each other, they will pull the N and C terminals together, and an intact fluorescent protein can be reconstituted to emit the fluorescent light.” Hu said.

Connected proteins are visible because of the fluorescence, but scientists can use the rapid mass spectrometry to identify the kinases. Researchers tested their method on a library of 559 human kinases and were able to identify new kinases against the library and confirm them through other biochemical assays.

Tao said the method they reported here integrates two cutting-edge biochemical techniques to enable successful identification of potential protein kinases of substrates (e..g, oncogenic proteins). The method is universal and can be used for the screening of novel protein kinases of any protein substrate. For the next step, they are working with proteins involved in late-stage cancer development. Most of their kinases are not known.

The National Institutes of Health, the National Science Foundation and the Purdue Center for Cancer Research supported the research. 

Featured Stories

Dog outdoors drinking water
Keeping your pets safe during the dog days of summer

As temperatures and humidity rise across the U.S., Candace Croney, director of the Center for...

Read More
Eastern hellbender salamanders feeding on bloodworms in their raceway at the Purdue Hellbender the Hellbender lab.
Metazoa Beer to Benefit Help the Hellbender Lab

Metazoa Brewing Company and the Indiana Lakes Management Society have teamed up to collaborate on...

Read More
Sonling Fei in front of digital trees
Digital forestry can help mitigate and prevent wildfires

The National Interagency Fire Center reports that, as of this writing, 19,444 fires have burned...

Read More
tomas hook next to boat
What you can do this summer to reduce the spread of aquatic invasive species

In 2020, an alligator was captured in a lagoon of Chicago’s Humbolt Park. The reptile out...

Read More
Researcher uses pipette on parsley plant
Researchers examine nanotechnological methods for improving agriculture

Nanoscale particles could potentially help address agricultural and environmental sustainability...

Read More
Fairgoers ride a tractor, sponsored by the Indiana Soybean Alliance, and browse food tents during the 2023 Indiana State Fair. (Purdue Agricultural Communications photo)
Purdue Extension to present engaging art and nature demonstrations at Indiana State Fair

The Indiana State Fair kicks off Aug. 2 and highlights the theme “The Art & Nature of...

Read More
To Top