AIDSWEEKLY Plus; Monday, December 3, 2007
Staff Medical Writers

An important step in the lifecycle of HIV—and a potential point of attack for treatment—is as follows: The viral RNA produced in the nucleus of the host cell is transported as a long strand out through pores in the cell membrane into the cell’s cytoplasm, where it is translated into proteins or packed into a viral shell. This discharge is an active process carried out by a viral protein called Rev. For this process, many Rev units have to attach to a binding site on the viral RNA, called the Rev-responsive element (RRE). The search for an effective RRE-binding inhibitor has thus far remained unsuccessful.

A small arginine-rich domain consisting of 17 amino acids allows the Rev protein to recognize its binding site, a furrow on the RNA. Once bound to the RNA, this domain adopts a helical form. It is this protein structure that the team led by John A. Robinson and Gabriele Varani wished to reverse engineer in order to disrupt the binding of Rev to RRE.

The researchers produced a peptide mimetic, a molecule that imitates the structure of the desired peptide. The group has previously shown that ¦Á-helical peptides can be imitated by something called a ¦Â-hairpin turn. The researchers attached side chains to the robust scaffold formed by the "hairpin?so that the groups of atoms required for molecular recognition are presented just as they are in the original helical peptide.

A series of screening steps, starting from a small family of cyclic hairpin peptide mimetics, led to the development of a structure that firmly and correctly binds RRE. This compound also has the ability to displace the Rev protein from Rev-RRE complexes.

"Hairpin peptide mimetics are a highly promising new class of drugs,?says Robinson. "We hope that it will be possible to develop a drug suitable for HIV treatment based on this foundation.? (2643 characters)

Keywords: HIV/AIDS, AIDS, Acquired Immunodeficiency Syndrome, HIV, Human Immunodeficiency Virus, Virology, John Wiley & Sons Inc.

This article was prepared by AIDS Weekly editors from staff and other reports.

2007-12-03
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