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Chemical biology

Greasy tags for protein removal

Nature volume 487, pages 308–309 (2012)Cite this article

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Most proteins in the human body are difficult targets for small-molecule drugs. This problem may have been overcome with the discovery of molecules that induce protein degradation, suggesting fresh, modular approaches to drug discovery.

It was recently discovered1,2 that proteins covalently 'tagged' with small, synthetic, hydrophobic molecules are degraded by the cell's quality-control machinery. Writing in Chemistry & Biology, Long et al.3 now report that non-covalent binding of such molecules also marks proteins for degradation. This finding could open up a wide range of proteins as targets for drug-discovery programmes.

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Figure 1: Hydrophobic tags for protein degradation.

References

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Authors and Affiliations

  1. Taavi K. Neklesa and Craig M. Crews are in the Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.,

    Taavi K. Neklesa & Craig M. Crews

  2. C.M.C. is also in the Departments of Chemistry and of Pharmacology, Yale University.,

    Craig M. Crews

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  1. Taavi K. Neklesa
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  2. Craig M. Crews
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Correspondence to Craig M. Crews.

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Neklesa, T., Crews, C. Greasy tags for protein removal. Nature 487, 308–309 (2012). https://doi.org/10.1038/487308a

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