Scientists Discover Common Blueprint for Protein Antibiotics

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Findings from the Los Angeles Biomedical Research Institute could enable a new generation of anti-infectives.

On March 18, 2019, researchers at the Los Angeles Biomedical Research Institute (LA BioMed) announced that they have found a common blueprint for proteins that have antimicrobial properties. According to the researchers, this discovery could enable the design and development of a new generation of anti-infectives active against pathogens that have become resistant to conventional antibiotics.

The findings, published in the Proceedings of the National Academy of Sciences of the United States of Americain a paper titled, “A Unifying Structural Signature of Eukaryotic α-helical

Host Defense Peptides,” suggest that certain peptides (small proteins) have antimicrobial activity if they contain a specific structural signature consisting of a conserved amino acid pattern that forms a three-dimensional shape known as an alpha-helix.

The discovery was made by Dr. Nannette Yount and Dr. Michael Yeaman, a professor of medicine at UCLA and chief of the Division of Molecular Medicine at Harbor-UCLA Medical Center, respectively. Yount and Yeaman discovered and characterized the alpha-core signature, and then used it to mine the database of all known proteins and peptides. As a result, they found thousands of proteins never before known to have antimicrobial activity. The team then synthesized examples of the newly discovered peptides demonstrating that they have potent antimicrobial activity against infective microbes that resist even the most modern antibiotics.

According to LA BioMed, Yeaman and Yount worked with Gerard Wong-a professor in the Department of Bioengineering, Department of Chemistry, and the California NanoSystems Institute at UCLA-his team from the Department of Bioengineering, Department of Chemistry and Biochemistry, and the California NanoSystems Institute at UCLA to further validate the significance of this discovery. Together, they applied artificial intelligence and machine learning methods to verify how the alpha-core signature encompasses features of peptides known to exert strong antimicrobial activity.

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The team also discovered that the alpha-core signature can be used to engineer fundamentally new types of anti-infectives designed to prevent or treat antibiotic-resistant microbes commonly found in hospitals and other healthcare facilities. LA BioMed has patented the intellectual property resulting from the discovery and holds the rights to the technology along with Yount and Yeaman.

“We are already nearing the clinic with molecules that incorporate this molecular signature and this discovery opens the door to thousands of new templates from which we can develop newer, potentially even better anti-infectives,” Yeaman said in a press release.

Source: LA BioMed