Fighting HIV, SARS
Carnegie Mellon University chemists have created a synthetic form of a cyclic peptide known for its remarkable ability to combat a wide variety of pathogens, including HIV and SARS.
Synthetic peptides like the one developed at Carnegie Mellon could provide an exciting new class of pharmaceuticals aimed at combating hard-to-treat diseases.
Furthermore, the manufacturing technique developed by Associate Professor of Chemistry Danith Ly could further the study of cyclic peptides by making the molecules easier and less expensive to produce.
Peptides are short chains of amino acids joined together by peptide bonds. They can be arranged in a linear chain or in a ring that is held together at the center by cross-linked bonds.
Scientists have explored the therapeutic potential of peptides for decades.
"The problem with peptides is that they're small and floppy and, when they bind, they don't bind with high affinity or selectivity. If you take a linear peptide and inject it into the bloodstream the half-life is less than two minutes," said Ly, who is a member of CMU's Center for Nucleic Acids Science and Technology.
"Nature gets around this by making peptides circular. In addition, if you inject a cyclic peptide into the blood stream it doesn't get chewed up and degraded. Its half-life is 40 hours or more."
Cyclic peptides are some of the most fascinating peptides found in nature — most venoms and many plants used in traditional tribal medicines contain cyclic peptides.
These peptides are thought to have great therapeutic potential, but due to their elaborate structure, they have been difficult to recreate in large quantities.
In the current study, the CMU researchers focused on RTD-1, a cyclic peptide held together by three disulfide bonds. Found in rhesus macaques and baboons, it has a broad range of antibacterial, antifungal and antiviral capabilities.
Most notably, RTD-1 has been shown to inhibit HIV from entering cells — offering the primates immunity from HIV and AIDS.
Early humans also had RTD-1, but a genetic mutation some nine million years ago caused humans to stop producing the peptide.
"If we can reproduce this peptide, we possibly could treat a wide range of infections to which humans were once immune," Ly said.