Novel Bifunctional Molecules Trigger a Protective Immune Response

A novel class of synthetic small, bifunctional molecules has been shown to have excellent potential for treatment of such diverse diseases as prostate cancer and HIV infection.

In general the compounds are called "antibody-recruiting molecules (ARM)" with an additional identifier (H for HIV or P for prostate cancer) to indicate specificity. The molecules have the ability to bind simultaneously to anti-2,4-dinitrophenyl (DNP) antibodies that are already present in the human bloodstream and to a specific epitope on the target. In the case of HIV, the target is gp120, a component of the Env surface viral glycoprotein (found on the surface of both HIV and virus-infected cells), while on prostate cancer cells the target is prostate-specific membrane antigen (PSMA).

The drugs work by coating the target cells with a layer of anti-DNP molecules. The antibody coating triggers an immune response that results in destruction of the target. In HIV, the treatment has the further benefit that the blocking of gp 120 prevents the HIV virus from infecting host cells. Details of these studies were published in the October 9, 2009, and November 4, 2009, online editions of the Journal of the American Chemical Society (JACS).

"This is an entirely new approach to treating these two diseases, which are extraordinarily important in terms of their impact on human health,” said senior author Dr. David Spiegel, assistant professor of chemistry at Yale University (New Haven, CT, USA). "Instead of trying to kill the pathogens directly, these molecules manipulate our immune system to do something it would not ordinarily do."

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