Abstract
Over the past century, the use of organ transplantation to replace malfunctioning tissue has leapt from an impossibility to being a routine procedure. This development has hinged on the use of immunosuppressive agents, which prevent rejection of the transplanted tissue. The most potent immunosuppressive drugs employed today are natural products and derivatives thereof, whose discovery, elucidation of mode of action, and introduction into clinical use have been enabled by chemical synthesis. However, more recently, research focusing on immunosuppressive natural products has not been able to identify novel scaffolds for clinical use. Here we discuss examples of immunosuppressive natural products in clinical use, explore how synthesis has contributed to our understanding of the mode of action as well as fundamental biology, and how synthetic chemistry could provide a means for future developments in this area.
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Acknowledgements
Generous support by the ERC (CoG VINCAT 682002 to N.M.), the FWF (Projects P32607 and P35045) and the WWTF (Project LS21-010) is acknowledged. We are grateful to the University of Vienna and the Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM) for continued support of our research programmes. We also thank S.S. Strohmenger and L.M. Gail (both CeMM) for fruitful discussions and helpful input.
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Schupp, M., Saridakis, I., Kaiser, D. et al. Chemical synthesis as a discovery platform in immunosuppression and determination of mode of action. Nat. Synth 3, 162–174 (2024). https://doi.org/10.1038/s44160-023-00423-2
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DOI: https://doi.org/10.1038/s44160-023-00423-2