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Breakthrough in cyclic peptide synthesis could accelerate antibiotic development

Scientists at King’s College London have developed a rapid method for creating cyclic peptides, potentially accelerating the production of new antibiotics to combat antimicrobial resistance (AMR). The research, published in the Journal of the American Chemical Society [1], demonstrates a technique that reduces synthesis time from hours or days to mere minutes.

Cyclic peptides: A crucial class of antibiotic molecules

Cyclic peptides, consisting of amino acid chains joined in a circular structure, are an important class of antibiotic molecules. However, their complexity has historically posed challenges in laboratory replication, hindering antibiotic development efforts.

Cyclosporine 3D

Breakthrough inspired by nature

The team studied a naturally produced cyclic peptide with promising activity against Mycobacterium tuberculosis, the causative agent of tuberculosis. They discovered that utilising the encoded amino acid sequence from the natural peptide allowed synthetic peptides to rapidly form cycles.

The team believes this simple approach can be used to make modified versions of the molecules used in antimicrobials, which can be used to develop new antibiotics.

Dr Sarah Barry, lead author from the Department of Chemistry at King’s College London, commented: “The global rise in antimicrobial resistant infections is putting the huge gains in modern medicine over the last century at risk. Everything from a cut in your finger to major surgery or cancer treatment requires the use of antibiotics. But when bacteria and viruses evolve to evade these medicines, these life-saving drugs lose their effectiveness.”

Potential applications beyond antimicrobials

Whilst the primary focus was on antimicrobials, the researchers successfully tested this process on various peptides, suggesting potential applications in other drug discovery areas, including anti-cancer agents.

Dr Yaoyu Ding, Research Assistant, said: “We have made a key part of the chemistry involved in making these molecules far easier and quicker. We hope that this chemistry will enable researchers to make libraries of derivates to enable screening for new antimicrobials.”

Implications for clinical laboratory scientists

This breakthrough could significantly impact the work of clinical laboratory scientists involved in antibiotic development and AMR research. The ability to rapidly synthesise and modify cyclic peptides may accelerate the screening and identification of novel antimicrobial compounds, potentially leading to more efficient drug discovery pipelines.

1. Yaoyu Ding, Edward Lambden, Jessica Peate, et. al. Rapid Peptide Cyclization Inspired by the Modular Logic of Nonribosomal Peptide Synthetases. Journal of the American Chemical Society 2024 146 (24). doi: