Peptoids Show Potential as Anti-Cancer Drugs

A recent publication described the preparation and purification of small oligomers called peptoids that mimic the ability of natural antibodies to bind and block vascular endothelial growth factor receptor 2 (VEGFR2), a membrane protein required by cancer cells for the generation of new blood vessels.

Peptoids, or N-substituted glycines, are closely related to their natural peptide counterparts, but differ chemically in that their side chains are appended to nitrogen atoms along the molecule's backbone, rather than to the alpha-carbons (as they are in amino acids). Peptoids are resistant to stomach enzymes so they could be taken orally. They are much less expensive and easier to manufacture than antibodies, and being much smaller than antibodies, they have greater potential to penetrate tumors or other disease sites.

In the current study, investigators at the University of Texas Southwestern Medical Center (Dallas, USA) prepared and screened more than 300,000 peptoid molecules. Using fluorescent microscopy they identified and isolated five peptoids that bound tightly to VEGFR2. Results published in the April 2, 2008, online edition of the Journal of the American Chemical Society revealed that one of the peptoids blocked VEGFR2's action in cultured cells. Furthermore, when administered in low doses to mice with implanted human bone- and soft-tissue cancer, the peptoid slowed the growth of the tumors and reduced the density of blood vessels leading to them.

"This new technique of rapidly isolating biologically active peptoids offers a way to hasten the drug-discovery process and may ultimately benefit patients by providing them with new therapies at a fraction of the cost of current drugs,” said senior author Dr. Thomas Kodadek, professor of internal medicine at the University of Texas Southwestern Medical Center. "Many new drugs being made today are antibodies, but they are extremely expensive to make. Financially, the U.S. health care system is going to have a difficult time accommodating the next 500 drugs being antibodies. Our results show that a peptoid can attack a harmful receptor in the body with the same precision as an antibody, but would cost much less to develop.”


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University of Texas Southwestern Medical Center