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CHEMICAL BIOLOGY

Diverse engineering

Nature Chemistry volume 11, pages 499–500 (2019)Cite this article

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Methods for generating molecular diversity provide a route to screen a wider section of chemical space, to discover compounds with useful biological properties. Now, a complexity-to-diversity strategy has enabled the discovery of a multi-cyclic structure from a complex natural product that induces ferroptotic cell death in cancer cells.

Natural products and synthetic small molecules provide the means to dissect and manipulate biological processes with spatial and temporal resolution. The identification of biologically active small molecules by high-throughput screening remains limited by the lack of structural diversity and the restricted three-dimensional complexity of compounds that can be found within traditional chemical libraries. To address this, a number of strategies have been designed that produce collections of structurally diverse and complex small molecules1. For instance, such approaches have led to the development of new scaffolds that are not found in nature, the identification of chemical probes that can modulate protein functions in unique ways, and the discovery of potentially druggable targets2. Another valuable strategy to identify new biologically active compounds is to produce libraries of molecules inspired by complex natural product scaffolds3. Now, writing in Nature Chemistry, Paul Hergenrother and co-workers have established a powerful complexity-to-diversity strategy4, which they use to fabricate small molecules with a diverse range of structures. These natural product-derived multi-cyclic structures can possess interesting and potent biological activity.

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Fig. 1: Complexity-to-diversity strategy reveals a novel thioredoxin inhibitor and inducer of ferroptosis.

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Authors and Affiliations

  1. Institut Curie, Paris, France

    Tatiana Cañeque & Raphaël Rodriguez

  2. CNRS UMR 3666, Paris, France

    Tatiana Cañeque & Raphaël Rodriguez

  3. INSERM U1143 , Paris, France

    Tatiana Cañeque & Raphaël Rodriguez

  4. PSL University Paris, Paris, France

    Tatiana Cañeque & Raphaël Rodriguez

Authors
  1. Tatiana Cañeque
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  2. Raphaël Rodriguez
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Correspondence to Raphaël Rodriguez.

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Cañeque, T., Rodriguez, R. Diverse engineering. Nat. Chem. 11, 499–500 (2019). https://doi.org/10.1038/s41557-019-0269-y

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