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Polypeptide Drug Stops HIV Replication

By Biotechdaily staff writers
Posted on 19 Nov 2007
AIDS researchers have developed a polypeptide drug that stops the spread of HIV by mimicking a critical region of the protein that mediates viral RNA transport.

Investigators at the University of Zurich (CH) and the University of Washington (Seattle, USA) searched for a small molecule that would inhibit the activity of the viral protein Rev, which actively transports HIV RNA from the nucleus of an infected cell into the cytoplasm. More...
The key to Rev function is an arginine-rich domain consisting of 17 amino acids that allows the Rev protein to recognize its binding site, a furrow on the RNA. During the transport process many Rev units attach to the binding site on the viral RNA, called the Rev-responsive element (RRE).

Rather than building an artificial peptide with the same 17 amino acids, the investigators screened a peptide library for a molecule that would mimic the three-dimensional structure adopted by this peptide region in the native protein. They eventually found a peptide with a "beta-hairpin” structure that mimicked the alpha-helix structure of the native protein region. Data published in the September 24, 2007, online edition of Angewandte Chemie revealed that after some chemical modification the peptide firmly and correctly bound RRE. Furthermore, this compound had the ability to displace the Rev protein from Rev-RRE complexes.

Dr. John A. Robinson, professor of organic chemistry at the University of Zurich, said, "Hairpin peptide mimetics are a highly promising new class of drugs. "We hope that it will be possible to develop a drug suitable for HIV treatment based on this foundation.”


Related Links:
University of Zurich
University of Washington

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