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Potent peptides inhibit HIV entry into cells
Date:10/10/2007

UPTON, NY -- 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
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
Source:Eurekalert

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