High-throughput screening articles within Nature Chemistry

Featured

  • Research Briefing |

    A protein-templated selection approach has been developed for the discovery of full ligands from dual-pharmacophore DNA-encoded libraries by incorporating fragment linking into the selection process. The performance of this method was demonstrated with selections against protein–protein interaction and protein–DNA interaction targets, through which potent and selective inhibitors were identified.

  • Article |

    Dual-pharmacophore DNA-encoded chemical libraries enable the identification of two synergistic binders for a biological target, but subsequent linking of this pair is required to obtain a full ligand, which can be challenging. Here we report a protein-templated selection of DNA-encoded dynamic library that can identify full ligands from fragment libraries without the need for subsequent fragment linking.

    • Yu Zhou
    • , Wenyin Shen
    •  & Xiaoyu Li

  • Article
    | Open Access

    In vitro screening of a ribosomally synthesized macrocyclic peptide library containing cyclic γ2,4-amino acids (cγAA) afforded the discovery of potent inhibitors of the SARS-CoV-2 main protease (Mpro). A co-crystal structure revealed the contribution of this cγAA to Mpro binding and the proteolytic stability of these macrocycles.

    • Takashi Miura
    • , Tika R. Malla
    •  & Hiroaki Suga

  • Perspective |

    DNA-encoded libraries can be applied in a diverse range of applications beyond simple binding assays. This Perspective covers the recent progress in using DNA-encoded chemical libraries to investigate complex biological targets and discusses their potential to identify structures that elicit function or possess other useful properties.

    • Yiran Huang
    • , Yizhou Li
    •  & Xiaoyu Li

  • Article |

    A method to label membrane proteins with a DNA tag has been developed that enables the selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells. As a demonstration, a 30-million-compound DNA-encoded chemical library is screened against folate receptor, carbonic anhydrase 12 and epidermal growth factor receptor on live cells.

    • Yiran Huang
    • , Ling Meng
    •  & Xiaoyu Li

  • Article |

    Dynamic nonlinear biochemical circuits are functionally rich; however, this nonlinear nature also makes programming them delicate and painstaking. Now a droplet microfluidic platform reveals precisely the bifurcations of two canonical systems: a bistable switch and a predator–prey oscillator, exposing optimal regions and mechanistic insights that inform the design of these systems.

    • A. J. Genot
    • , A. Baccouche
    •  & Y. Rondelez

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