Skip to main content
SpringerLink
Log in

NSMB’s 30th anniversary

Chemical rewiring of ubiquitination by degraders and their selectivity routes

  • Comment
  • Published:

From Nature Structural & Molecular Biology

View current issue Submit your manuscript

This article has been updated

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

Change history

  • 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).

Author information

Authors and Affiliations

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

    Rory Whelan & Cristina Mayor-Ruiz

Authors
  1. Rory Whelan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristina Mayor-Ruiz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cristina Mayor-Ruiz.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41594-024-01215-8

  • Springer Nature America, Inc.

Search

Navigation