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Scientists Develop 'Super Peptide' That Kills Candida Albicans

  [ 255 votes ]   [ Discuss This Article ] • April 28, 2003

Zengen, Inc. announced that its scientists have developed a 'super' peptide that kills Candida albicans (C. albicans), a single-celled organism that is the most prevalent yeast species in the human gastrointestinal (GI) tract. A common fungus, C. albicans causes a variety of infections, including vaginitis. This organism can invade tissues and produce fatal infections in individuals with compromised immune systems such as those suffering from HIV/AIDS or undergoing organ or bone transplants.

This discovery, say the researchers, may also be a key to understanding one of the greatest mysteries of Mother Nature -- how a peptide that has existed in the same form since at least the Pennsylvanian period of the Paleozoic era (more than 300 million years ago) really works in modulating inflammatory and immune responses.

The study, "Novel alpha-Melanocyte Stimulating Hormone Peptide Analogues with High Candidacidal Activity," is scheduled to appear in the February 20, 2003 issue of the Journal of Medicinal Chemistry, a peer-reviewed journal of the American Chemical Society, the world's largest scientific society.

Scientists aimed to find alpha-MSH analogues with greater antimicrobial activity and to reach a better understanding of the peptide structure-antifungal activity relations against C. albicans through design, synthesis and testing of novel peptide analogues in which several modifications were made. Because previous data suggested that antimicrobial effects of alpha-MSH were receptor-mediated, the research team chose to focus on the alpha-MSH amino acid sequence (6-13), which contains the invariant core sequence His-Phe-Arg-Trp (6-9) that is important for binding to the known melanocortin receptors. A second focus was on the sequence Lys-Pro-Val (11-13) that is known to be important for antimicrobial activity.

In this structure-activity study, the team developed several compounds that have greater candidacidal activity than alpha-MSH and, in fact, one particular peptide (number 19) killed nearly 100 percent (99.7 percent) of Candida cells over repeated experiments. Further, results indicate that substitutions in the alpha-MSH (6-13) amino acid sequence can either enhance or reduce candidacidal influences of the peptide. This discovery may help scientists understand the unique mechanism of action of alpha-MSH peptides, which are substantially different from that of most antimicrobial agents that cause direct damage to the microbial membrane.

"The power of this new alpha-MSH analogue against C. albicans appears to be significantly greater than any other known peptides, as it is super-potent, super-stable and super-durable," stated Paolo Grieco, Associate Professor, Department of Pharmaceutical Chemistry and Toxicology, University of Naples, Italy, and lead author on the paper. "We've not only improved upon Mother Nature by developing a 'super' peptide that kills C. albicans, but also may have unlocked the key to understanding how alpha-MSH really works -- through a receptor in yeast which is yet to be identified."

Unlike viruses or bacteria, fungal cells such as yeast resemble the cells of the human body and thus, can be difficult to treat. There is increasing evidence that C. albicans strains become resistant to current treatments -- enabling these fungi to take on 'super' powers.

"This new peptide analogue appears to be different from the known anti-microbial peptides, such as alpha-MSH, that have been around for hundreds of millions of years," said Ettore Novellino, Professor and Dean of the Faculty of Pharmacy, University of Naples, Italy, and co-author of the paper. "Clearly there is more research to be conducted on Zengen's novel molecules and we are excited about the enormous clinical implications of our discovery."

Zengen's proprietary molecules were developed from more than 25 years of original research in the US, Europe and Asia on peptide molecules derived from alpha-Melanocyte-Stimulating Hormone (alpha-MSH). A naturally occurring molecule, alpha-MSH modulates inflammatory and immune responses. James Lipton, Ph.D., Zengen's chief scientific officer, chairman of the scientific advisory board and director, and his collaborators first demonstrated that alpha-MSH possesses anti-inflammatory properties and uncovered the specific activity of the carboxy-terminal tripeptide region (C-terminal peptide) of the alpha-MSH peptide. These discoveries led to the development of Zengen's proprietary peptide molecules, including CZEN 002, a synthetic octapeptide. Zengen is currently conducting phase I/II clinical trials with CZEN 002 in vaginitis.

"Ultimately these new findings, coupled with results from ongoing research with our proprietary molecules, such as our clinical trials in vaginitis with CZEN 002, could lead to the development of valuable pharmaceutical agents to control yeast growth," added Dr. Lipton, study co-author. "This holds tremendous promise to change the way inflammatory and infectious diseases are treated."


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