Cyclic peptides can bind challenging disease targets, but their oral application is hindered by digestion and absorption issues. We developed a versatile method for the synthesis and functional screening of vast numbers of synthetic cyclic peptides and identified peptides with high inhibitory activity, stability and oral bioavailability in rats.
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References
Scott, D. E. et al. Small molecules, big targets: drug discovery faces the protein–protein interaction challenge. Nat. Rev. Drug. Discov. 15, 533–550 (2016). This review article discusses challenging disease targets and their structural features.
Naylor, M. R. et al. Cyclic peptide natural products chart the frontier of oral bioavailability in the pursuit of undruggable targets. Curr. Opin. Chem. Biol. 38, 141–147 (2017). This review article presents cyclic peptides identified in nature that are orally available.
Habeshian, S. et al. Synthesis and direct assay of large macrocycle diversities by combinatorial late-stage modification at picomole scale. Nat. Commun. 13, 3823 (2022). This paper describes a method for nanoscale synthesis and high-throughput screening of disulfide-cyclized peptides.
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This is a summary of: Merz, M. L. et al. De novo development of small cyclic peptides that are orally bioavailable. Nat. Chem. Biol. https://doi.org/10.1038/s41589-023-01496-y (2023).
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Development of cyclic peptides that can be administered orally to inhibit disease targets. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01505-0
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DOI: https://doi.org/10.1038/s41589-023-01505-0
