A Yale University lab has crafted the first synthetic¹ molecules² that have both the targeting and response functions of antibodies. The new molecules -- synthetic antibody mimics³ (SyAMs) -- attach themselves simultaneously⁴ to disease cells and disease-fighting cells. The result is a highly targeted immune response, similar to the action of natural human antibodies.

 

"Unlike antibodies, however, our molecules are synthetic organic compounds that are approximately one-twentieth the size of antibodies," said David A. Spiegel, a professor of chemistry at Yale whose lab developed the molecules. "They are unlikely to cause unwanted immune reactions due to their structure, are thermally⁵ stable, and have the potential to be administered orally, just like traditional, small-molecule drugs."

 

Spiegel and his team describe the research in a paper published online Dec. 16 by the Journal of the American Chemical Society.

 

The paper looks specifically at SyAM molecules used to attack prostate cancer. Called SyAM-Ps, they work first by recognizing cancer cells and binding⁷ with a specific protein on their surface. Next, they also bind⁶ with a receptor on an immune cell. This induces a targeted response that leads to the destruction of the cancer cell.

 

Spiegel said the process of synthesizing and optimizing⁸ the structure of the molecules required considerable time and effort. "We now know that synthetic molecules of intermediate size possess perhaps the most important functional⁹ properties of antibodies -- targeting and stimulation¹⁰ of immune cells," he said.

 

"It's also noteworthy that molecules of such a small size can bring together two objects as enormous as cells, and trigger a specific functional response, entirely¹¹ as a result of specific receptor interactions," Spiegel added.

 

Beyond their potential for treating prostate cancer, SyAMs may have applications for treating other forms of cancer, HIV and various bacterial¹² diseases.

 

Spiegel also is a member of Yale Cancer Center.

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