Chemical biology

Chemical biology is the study of the chemicals and chemical reactions involved in biological processes, incorporating the disciplines of bioorganic chemistry, biochemistry, cell biology and pharmacology. Chemicals – including natural small molecules, such as lipids, carbohydrates and metals, or non-natural probe or drug molecules – are used to gain insight into biological problems at a mechanistic level.

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  • Research Highlights |

    Smith et al. report the design of ripretinib, an investigational tyrosine kinase inhibitor that forces the activation loop of KIT and PDGFRα into an inactive conformation and targets a broad spectrum of KIT and PDGFRα mutants in GIST.

    • M. Teresa Villanueva
  • News and Views |

    A synthetic DNA enzyme catalyses the formation of a native phosphodiester bond between two RNA fragments, but the molecular details of the mechanism remained elusive. Research using computational and biochemical approaches now suggests that the DNA enzyme recruits two magnesium ions to assist in the catalysis of RNA ligation.

    • Claudia Höbartner
    Nature Catalysis 2, 483-484
  • News and Views |

    Hydrogenases are very powerful biocatalysts for dihydrogen cleavage. Now, X-ray crystallography shows how [Fe]-hydrogenase requires ligand exchanges at the metal centre and significant molecular motions to open and close its active site to effectively transfer a hydride to an electrophilic organic substrate.

    • Yvain Nicolet
    Nature Catalysis 2, 481-482
  • News and Views |

    The biological functions of glycan motifs such as the Lewis blood antigens are often defined by their precise multivalent presentation on complex glycoconjugates, making synthesis particularly challenging. Access to a number of positionally defined Lewis motifs on natural polysaccharide scaffolds has now been achieved using bacterial glycosyltransferases.

    • Kun Huang
    •  & Sabine L Flitsch
    Nature Catalysis 2, 479-480
  • News and Views |

    The concept that resistance against androgen receptor (AR) signalling inhibitors is explained by AR variants (ARVs) has spread as a seductive meme. However, two problems have delayed the translation of these findings to clinical practice: the complexity of the mechanism of action and the challenging development of clinical decision-making tools involving ARVs.

    • Florian Handle
    •  & Frank Claessens