Potent Peptides Inhibit HIV Entry Into Cells
|
Tweet
|
|
Based in part on protein structures determined at the National Synchrotron Light Source (NSLS) at the U.S. Department of Energy’s Brookhaven National Laboratory, scientists at the University of Utah have developed new peptides that appear to be significantly more effective at blocking HIV’s entry into cells than other drugs in their class.
In a paper being published online by the Proceedings of the National Academy of Sciences the week of October 8, 2007, the researchers say these peptides are sufficiently potent to begin pre-clinical studies as a new class of agents for the prevention and treatment of HIV/AIDS.
"Our ‘D-peptides’ offer several potential therapeutic advantages over existing peptide entry inhibitors, which are costly, require high dose injections, and suffer from the emergence of drug-resistance,” said University of Utah biochemist Michael S. Kay, lead author on the paper. “In contrast, our D-peptides resist degradation, so they have the potential to be administered by mouth and last longer in the bloodstream. Since these inhibitors have a unique inhibitory mechanism, they should work well in combination with existing HIV inhibitors.”
The researchers were particularly interested in developing drugs to bind to an essential “pocket” structure found in all HIV strains that was previously identified as a promising drug target using structures determined at Brookhaven’s NSLS. Numerous previous attempts to target this pocket failed to produce potent and non-toxic pocket-specific entry inhibitors. In the current work, the researchers used a high-throughput technique to screen a “library” containing hundreds of millions of peptides to identify the rare peptides that would bind to the pocket structure and inhibit HIV entry.
After identifying the most promising candidate peptides, the researchers analyzed the structure of these peptides bound to the target protein using x-ray crystallography at the NSLS. In this technique, researchers analyze how an extremely bright beam of x-rays, available only at synchrotron sources, bounces off and is refracted by the sample to determine the positions of individual atoms. “These structures reveal details of how the peptides bind and guide the development of future inhibitors,” said paper co-author Annie Heroux, a biologist and crystallography specialist at Brookhaven Lab.
This structure-assisted design led to the discovery of D-peptides with up to a 40,000-fold improved antiviral potency over previously reported D-peptides. The structures also suggest ways to engineer the peptides to reduce the chance of drug resistance.
This research was funded by the National Institutes of Health, the University of Utah Technology Commercialization Project, and by the American Cancer Society. Operational funding for the NSLS is provided by the Office of Basic Energy Sciences within the U.S. Department of Energy’s Office of Science and by the National Institutes of Health.
Note to local editors: Annie Heroux lives in Shirley, New York.
University of Utah contact: Phil Sahm, 801 581-2517,
 |
 |
 |
 | ||
| RELATED STORIES: | ||
| Comments | [ + Post Your Own ] |
Now you're in the public comment zone. What follows is not Armenian Medical Network's stuff; it comes from other people and we don't vouch for it. A reminder: By using this Web site you agree to accept our Terms of Service. Click here to read the Rules of Engagement.
There are no comments for this entry yet. [ + Comment here + ]
We are pleased to let readers post comments about an article. Please increase the credibility of your post by including your full name and email.
All comments are reviewed by our editors before they are posted on the site. Just keep it clean, kids.
