Trends in Peptide Science and Stapled Peptides in the UK

The UK has long had a strong peptide science community. This is evidenced in part by a busy conference schedule and the activities of the Peptide and Protein Science Group (PPSG) and Chemical Biology and Bio-organic Chemistry Group (CBBG) of the Royal Society of Chemistry.

There are also a number of prestigious research groups in the country with particular strengths in peptide science. These include the Peptide and Protein Science Group and the Centre for Biomolecular Sciences at University College London, the Centre for Biomolecular Sciences at Manchester and the Institute of Genetics and Molecular Medicine at Edinburgh.

A recent trend in peptide science is the development of stapled peptides. This method involves replacing the disulphide bonds in a protein sequence with nitrogen-nitrogen bridges (N-N), thereby reducing the energy required for binding to a target protein and increasing the specificity of the interaction. The articles in this special issue all focus on the application of stapled peptides to different targets.

The first article, by Professor Mark Bradley’s group at the University of Edinburgh, synthesised fluorescently tagged antimicrobial peptides that were shown to successfully label fungal and bacterial species in a mammalian cell-line, using fluorescent confocal microscopy. The authors suggest that the peptides could be used to rapidly identify infected tissue samples, potentially enabling early and cost-effective diagnosis of infection in clinical settings.

In the next article, Dr Craig Jamieson from the University of Strathclyde developed a series of stapled peptide mimics of the human voltage-gated sodium channel m-conotoxin KIIIA. These analogues were shown to be biologically active by NMR spectroscopy, and further structural analysis revealed that the stapled peptides were capable of blocking channel gating.

Finally, Dr Chris Coxon from Heriot-Watt University developed a two-level factorial design approach to optimise reaction conditions for the stapling of peptides with hexafluorobenzene. This was applied to the synthesis of a model stapled peptide, CJC 1295. The resulting peptide was sold in the ‘Health and Personal Care’ section on Amazon with a main image containing cynical warnings that the product is a’research peptide not for human consumption’ and the description asserting that it will ‘increase muscle mass, strength and speed up post-training recovery’.

The final article in this special issue, by Professor John Howl at the University of Wolverhampton, covers the emerging area of bioportides – bi-functional sub-classes of cell penetrating peptides that act as regulators of protein-protein interactions. The stapling strategy used here is particularly promising and provides a good example of the scalability of stapled peptide chemistries to new targets. A further review article, by Professor Alison Hulme from the University of Glasgow, examines the lessons that can be learned from available crystal structures of stapled peptides bound to their target proteins. This work will help to guide future stapled peptide chemistries towards improved biological activity and stability. The ‘grey market’ for novel synthetic peptide hormones (SPH) is readily accessible through sellers on mainstream e-commerce platforms like Amazon, eBay and Alibaba in the UK. Despite this, a large proportion of the products being sold continue to carry cynical warnings that they are’research peptides not for human consumption’ or ‘for research use only’. uk peptides

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