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Chemical rewiring of ubiquitination by degraders and their selectivity routes

Nature Structural & Molecular Biology volume 31, pages 205–207 (2024)Cite this article

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Ubiquitination is an essential process that curtails cellular levels of damaged and redundant proteins. Chemical biologists have harnessed this natural system to induce the degradation of disease-relevant proteins. We reflect here on the potential of ‘degraders’ for targeted selectivity, and discuss the role of computer-aided drug design in shaping future advances.

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Fig. 1: The main modalities and advantages of targeted protein degradation.

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  • 04 March 2024

    In the version of the article initially published, an earlier, incorrect version of Fig. 1 was included. This has now been amended in the HTML and PDF versions of the article.

References

  1. Békés, M., Langley, D. R. & Crews, C. M. Nat. Rev. Drug Discov. 21, 181–200 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Domostegui, A., Nieto-Barrado, L., Perez-Lopez, C. & Mayor-Ruiz, C. Chem. Soc. Rev. 51, 5498–5517 (2022).

    Article  CAS  PubMed  Google Scholar 

  3. Bondeson, D. P. et al. Cell Chem. Biol. 25, 78–87.e5 (2018).

    Article  CAS  PubMed  Google Scholar 

  4. Gadd, M. S. et al. Nat. Chem. Biol. 13, 514–521 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ward, J. A., Perez-Lopez, C. & Mayor-Ruiz, C. ChemBioChem 24, e202300163 (2023).

    Article  CAS  PubMed  Google Scholar 

  6. Li, W. et al. PLoS One 3, e1487 (2008).

    Article  ADS  MathSciNet  PubMed  PubMed Central  Google Scholar 

  7. Belcher, B. P., Ward, C. C. & Nomura, D. K. Biochem 62, 588–600 (2023).

    Article  CAS  Google Scholar 

  8. Kirsch, P., Hartman, A. M., Hirsch, A. K. H. & Empting, M. Molecules 24, 4309 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gao, K., Oerlemans, R. & Groves, M. R. Biophys. Rev. 12, 85–104 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lucas, X., Van Molle, I. & Ciulli, A. J. Med. Chem. 61, 7387–7393 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kori, S. et al. Bioorg. Med. Chem. 52, 116500 (2021).

    Article  CAS  PubMed  Google Scholar 

  12. Ishida, T. & Ciulli, A. SLAS Discov. 26, 484–502 (2021).

    Article  CAS  PubMed  Google Scholar 

  13. Schneider, H. et al. Preprint at bioRxiv https://doi.org/10.1101/2023.09.29.558399 (2023).

Download references

Acknowledgements

We thank the European Research Council (ERC) (ERC-2021-StG-101040046), ‘la Caixa’ Foundation, FERO-ASEICA, AECC, the Mark Foundation for Cancer Research, the Spanish Ministry of Science and Innovation (PID2020-120110RA-I00 and RYC2020-030061-I), and AGAUR-GenCat (2021SGR01279).

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  1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Technology (BIST), Baldiri Reixac, Barcelona, Spain

    Rory Whelan & Cristina Mayor-Ruiz

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  1. Rory Whelan
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  2. Cristina Mayor-Ruiz
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Correspondence to Cristina Mayor-Ruiz.

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The authors declare no competing interests.

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Whelan, R., Mayor-Ruiz, C. Chemical rewiring of ubiquitination by degraders and their selectivity routes. Nat Struct Mol Biol 31, 205–207 (2024). https://doi.org/10.1038/s41594-024-01215-8

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