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New way to test cancer drugs

By R&D Editors | March 17, 2011

Purdue Proteins

Andy Tao uses nanopolymers and chemical reactions that cause color changes in a solution to detect activity related to cancer cell formation. Credit: Purdue Agricultural Communication photo/Tom Campbell

A Purdue
Univ. scientist’s
nanopolymer would make it easier and cheaper for drug developers to test the
effectiveness of a widely used class of cancer inhibitors.

W. Andy Tao, an associate professor of biochemistry
analytical chemistry and a member of the Purdue Center
for Cancer Research team, created the Purdue-patented pIMAGO nanopolymer that
can be used to determine whether cancer drugs have been effective against
biochemical processes that can lead to cancer cell formation. The nanopolymers
would attach themselves to target proteins that would later be detected by a
relatively simple laboratory procedure called chemiluminescence.

Tymora Analytical, a company Tao started in the Purdue Research
Park, will manufacture
the pIMAGO nanopolymers. The ‘p’ stands for phosphor, and the IMAGO comes from
the Greek word for image.

Tao’s pIMAGO nanopolymers are coated in titanium ions and
would attract and bond with phosphorylated proteins, ones in which a phosphate
group has been added to a protein activating an enzyme called kinase. Kinase,
when overactive, is known to cause cancer cell formation, and many cancer drugs
are aimed at inhibiting kinase activity.

“It is universal. You can detect any kind of phosphorylation
in a protein,” said Tao, whose findings were reported in the early online
version of Analytical Chemistry.
“It is also cheaper and would be more widely available.”

The nanopolymers would be added to a solution of proteins,
a chemical agent to start phosphorylation and a drug to inhibit kinase
activity. Phosphorylated proteins would only be present if the drug is
ineffective.

Avidin-HRP—the protein Avidin bound with the enzyme
horseradish peroxidase—would be added. Avidin would bind with a vitamin B acid
called biotin that is also on the nanopolymers’ surfaces. A chemical called a
substrate, added later, would cause a reaction with HRP, causing the solution
to change color.

A lightly colored solution would mean there had been little
kinase activity and few phosphorylated proteins and that the drug was
effective. A darker solution would signal more kinase activity and a less
effective drug.

“This could have a lot of applications in
pharmaceuticals for drug discovery,” Tao said.

Screening kinase inhibitors using antibodies can be
cost-prohibitive for many laboratories because antibodies are in short supply
and aren’t available for many types of cells. Radioisotope tests are highly
regulated and possibly dangerous because of radiation involved.

“We want to develop this as a commercial application
to replace radioisotopes and antibodies as a universal method for screening
kinase inhibitors,” Tao said.

SOURCE

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