A hairpin to fight HIV

Nov 02, 2007

When a host cell is infected with HIV, the virus brings its own genetic material into the host cell. This cell then replicates, reads the viral RNA, and uses it as a blueprint to produce more viral proteins.

Complete viruses are then released to attack the next cells. A team of researchers from the University of Zurich (Switzerland) and the University of Washington (USA) has now developed a new potential starting point for a drug that could intervene in this deadly cycle. As reported in the journal Angewandte Chemie, it involves a hairpin-shaped molecule that imitates the spatial structure of an important viral protein and should thus stop the discharge of viral RNA from the cell nucleus.

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 alpha-helical peptides can be imitated by something called a alpha-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?"

Source: John Wiley & Sons, Inc.

Explore further: Research pair devise a way to make nylon precursor that is less harmful to the ozone layer

add to favorites email to friend print save as pdf

Related Stories

Research reveals structure of key CRISPR complex

Dec 10, 2014

Using a gene-editing system originally developed to delete specific genes, MIT researchers have now shown that they can reliably turn on any gene of their choosing in living cells.

Pirate viruses caught in their own trap?

Dec 02, 2014

In order to infect a host cell and proliferate, some viruses, such as the hepatitis C virus, infiltrate the ribosomes, the molecular machines that assemble the proteins present in each of our cells. Viral ...

Computer model enables design of complex DNA shapes

Dec 03, 2014

MIT biological engineers have created a new computer model that allows them to design the most complex three-dimensional DNA shapes ever produced, including rings, bowls, and geometric structures such as icosahedrons that ...

Recommended for you

'Global positioning' for molecules

25 minutes ago

In everyday life, the global positioning system (GPS) can be employed to reliably determine the momentary location of one en route to the desired destination. Scientists from the Institute of Physical and ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.