Lead optimization articles within Nature Chemistry

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  • Article
    | Open Access

    Late-stage functionalization of complex drug molecules is challenging. To address this problem, a discovery platform based on geometric deep learning and high-throughput experimentation was developed. The computational model predicts binary reaction outcome, reaction yield and regioselectivity with low error margins, enabling the functionalization of complex molecules without de novo synthesis.

    • David F. Nippa
    • , Kenneth Atz
    •  & Gisbert Schneider

  • Article |

    The efficacy of carbapenem antibiotics can be compromised by metallo-β-lactamases, but a high-throughput screen followed by optimization has now enabled the discovery of indole-2-carboxylates (InCs) as potent broad-spectrum metallo-β-lactamase inhibitors. The results highlight the potential of InC–carbapenem combinations for clinical use as well as mechanism-guided approaches to combatting globally disseminated antibiotic resistant mechanisms.

    • Jürgen Brem
    • , Tharindi Panduwawala
    •  & Christopher J. Schofield

  • News & Views |

    The therapeutic applications of DNAzymes are limited because of their low effectiveness in vivo. Now, a promising approach for constructing DNAzymes that show high gene-silencing efficiency in mammalian cells has been developed. This approach incorporates chemical modifications into an existing DNAzyme scaffold.

    • Yifei Zhou
    •  & Chuanzheng Zhou

  • News & Views |

    A new click-style reaction based on a strain-release amination strategy has been developed. This approach can be used to append small, strained ring systems onto a core scaffold.

    • John A. Milligan
    •  & Peter Wipf

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