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Chemists devise new route to AIDS drugs.

Just as couturiers dream up innovative ways to fashion apparel, drug designers seek out novel routes for creating their compounds. The ingenuity of two such chemists may eventually pay off with less costly drugs for fighting AIDS.

Zidovudine, also known as AZT, currently represents the most effective AIDS treatment and the only one to gain FDA approval. AT Emory University in Atlanta, Michael W. Hager and Dennis C. Liotta have now developed a way to make zidovudine from simpler, less expensive starting materials. Their technique may also yield other, related compounds with antiviral activity, they suggest in the June 19 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY.

Zidovudine belongs to a class of compounds called nucleosides, which slow infection by interfering with viral replication. Chemists usually synthesize new nucleosides by modifying naturally existing ones. These natural nucleosides are costly to obtain, but their complex structure ensures that the end product has the right molecular shape. Past attempts to start with simpler materials have generally yielded nucleoside mixtures that included undesirable chemical variants, Liotta says.

He and Hager took a completely different tack that allowed them to avoid nucleosides altogether and to use starting materials that can be mass produced inexpensively. They changed the reaction conditions so that the useful version of zidovudine would form slightly faster than the undesirable versions and would not convert into those variants, Liotta explains. "We never thought it would be as selective as it is," he told SCIENCE NEWS.

Some companies developing nucleosides seem interested. "It's a very unique way of going about making nucleosides, and it allows access to a number of other compounds that may have potential anti-HIV activity," says Stanley A. Lang, a chemist with American Cyanamid Co. in Pearl River, N.Y. The company is looking into Liotta's approach as it develops an AZT-like drug called FLT, he says.

Liotta emphasizes that the recent experiments are just a first step. "Some things scale up well and some things don't," he says. "You really don't know what will happen."
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Title Annotation:a new, less expensive way to make zidovudine
Author:Pennisi, Elizabeth
Publication:Science News
Date:Jul 6, 1991
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