(ATN) CPFs: Researchers Design New Anti-HIV Compounds

(ATN) CPFs: Researchers Design New Anti-HIV Compounds

AIDS TREATMENT NEWS No. 108 - August 3, 1990
Michelle Roland

On July 20 researchers at the Dana-Farber Cancer Institute at Harvard Medical School, and at the Harvard University Department of Chemistry, reported the development of a new class of anti-HIV chemicals, in an article in Science magazine (Prevention of HIV-1 Infection and Preservation of CD4 Function by the Binding of CPFs to gp120. Finberg R.W. and others, Science, vol. 249, pages 287-291, July 20, 1990.) A brief flurry of news reports followed. While these chemicals are not yet ready for human tests, their development is important.

The new substances, called CPFs, are chemical variants of small peptides -- short fragments of amino acids, the building blocks of proteins. CPFs contain only two amino acids. They work like soluble CD4, binding to the gp120 molecules on the AIDS virus -- the molecules which attach to T-helper cells and allow the virus to enter. They may also protect the T-cells from being damaged by free gp120 in the blood.

In laboratory tests, the chemicals already developed required relatively high concentrations to protect cells against infection -- 40 micrograms/ml or more. A good antibiotic would usually work at lower concentrations -- suggesting that the CPFs already studied might not become useful drugs themselves. But the researchers have found that small changes in the molecule can make big differences in effectiveness, suggesting that better versions might be created in the future.

At this time, no one knows if humans can tolerate CPFs -- or if they will be stable in the body. But mice given 20 to 50 times the dose expected to be effective showed no toxicity, according to a UPI report based on a recent interview with one of the researchers.

CPFs may be important because:

* They were rationally designed to block a specific part of gp 120 which is essential for viral binding to T-helper cells (and other cells with the CD4 marker, which HIV apparently uses to gain entry into uninfected cells). Test after test has shown that CPFs behaved as expected in laboratory cultures. The existence of a clear rationale helps chemists design new versions of the chemical which may work better.

* HIV binding to uninfected cells seems to depend on a critical arrangement of molecules in the virus. Therefore, scientists expect that HIV may not be able to develop resistance to CPFs, as it appears to do with AZT-type drugs. If the virus mutates so that its gp 120 cannot bind to CPFs, then it may also be unable to bind to CD4 receptors and infect cells.

* Unlike soluble CD4, CPFs are easy and inexpensive to manufacture. And they could probably be given orally.

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