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Synthetic molecules may be less expensive alternative to therapeutic antibodies, researchers find
Date:4/4/2008

ors or other disease sites, he said.

Our technique is simple and fast, works with existing chemicals and needs no high-tech instrumentation, except for a microscope to detect the fluorescent colors we use to sort the compounds, said Dr. D. Gomika Udugamasooriya, postdoctoral researcher in internal medicine and lead author of the study.

The new technique also has major advantages over traditional screening techniques that are commonly used to discover biologically active compounds from large collections. These screens, which require extensive automation, generally cost $40,000 or more; the new method can be conducted for less than $1,000.

The researchers screened about 300,000 peptoids to see which ones would interact with VEGFR2, a type of molecule on the surface of human cells. VEGFR2 is essential in creating new blood vessels through interaction with the hormone VEGF, which is normally a helpful process but is harmful to the body when the new blood vessels are nourishing a growing tumor.

A commercially produced antibody is used to treat some cancers by blocking the VEGF-VEGFR2 interaction and thus starving the tumor, but it costs a patient about $20,000 a year, Dr. Kodadek said.

The new screening technology involves hundreds of thousands of peptoids, bound to tiny plastic beads. In the study, the cells with VEGFR2 were labeled to fluoresce red and those lacking VEGFR2 were labeled to fluoresce green. After exposing the beads to the mixture of cells, the beads were examined under a fluorescent microscope. Those bound to red cells the ones with VEGFR2 were collected.

This screen, which took a couple of days, isolated five peptoids out of approximately 300,000 screened, showing that the process was an effective way to quickly narrow down a search, Dr. Kodadek said.

The researchers further tested one of the five peptoids that bound most tightly to VEGFR2 and found that it blocked VEGFR2s action in
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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

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