CPFs: Researchers Design New Anti-HIV Compounds

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 RW 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.