A Hairpin To Fight HIV

Oct 29, 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 α-helical peptides can be imitated by something called a β-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.”

Citation: John A. Robinson, Design of β-Hairpin Peptidomimetics That Inhibit Binding of α-Helical HIV-1 Rev Protein to the Rev Response Element RNA, Angewandte Chemie International Edition, doi: 10.1002/anie.200702801

Source: Angewandte Chemie

Explore further: Scientists find clues to cancer drug failure

add to favorites email to friend print save as pdf

Related Stories

Study tries to detect flu before the first sneeze

Sep 21, 2009

(AP) -- Coughed on by somebody with the flu? Duke University researchers are developing a test to determine - with a mere drop of blood - who will get sick before the sniffling and fever set in. And they're ...

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.

Recommended for you

Scientists find clues to cancer drug failure

13 hours ago

Cancer patients fear the possibility that one day their cells might start rendering many different chemotherapy regimens ineffective. This phenomenon, called multidrug resistance, leads to tumors that defy ...

Smart crystallization

18 hours ago

A novel nucleating agent that builds on the concept of molecularly imprinted polymers (MIPs) could allow crystallographers access to proteins and other biological macromolecules that are usually reluctant ...

Supersonic electrons could produce future solar fuel

18 hours ago

Researchers from institutions including Lund University have taken a step closer to producing solar fuel using artificial photosynthesis. In a new study, they have successfully tracked the electrons' rapid transit through ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

pozgirl
not rated yet Oct 31, 2007
I wonder if this possible new treatment will be as expensive as the current ones. People on hiv personal and support site http://www.pozgroup.com always say that they can not afford the high expenditure of treatment. Especially some new drugs.

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.