Chemical biology articles within Nature

Featured

  • Article |

    Targeted protein relocalization using shuttle proteins with potent ligands amenable to incorporation into targeted relocalization activating molecules could be used to regulate cellular physiology and correct disease states in neurodegenerative diseases, cancer and genetic disorders.

    • Christine S. C. Ng
    • , Aofei Liu
    •  & Steven M. Banik

  • News & Views |

    Many diseases arise from the misplacement of proteins in cells. A potential solution to this problem has been developed: small molecules that help displaced proteins catch a ride with other proteins to return to their proper location.

    • Robert Yvon
    •  & Christina M. Woo

  • Article |

    A palladium-catalysed reaction converts hydrocarbon-derived precursors to chiral boron-containing nortricyclanes, and the shape of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings.

    • Mingkai Zhang
    • , Matthew Chapman
    •  & James P. Morken

  • News & Views |

    Proteins have been designed that assemble in different ways depending on whether an ‘effector’ molecule is present — a demonstration of allostery, the phenomenon that enables switch-like control of protein functions in nature.

    • A. Joshua Wand

  • Article
    | Open Access

    Structural analyses of analogues of stable ubiquitin transthiolation intermediates with E1, E2 and E3 enzymes reveal a population of intermediate states that provide insights into the directional transfer of ubiquitin between E1, E2 and E3.

    • Tomasz Kochańczyk
    • , Zachary S. Hann
    •  & Christopher D. Lima

  • Review Article |

    This Review examines the diverse strategies utilized by naturally occurring antibiotics and suggests how they have provided, and will in future provide, inspiration for the design of novel antibiotics.

    • Kim Lewis
    • , Richard E. Lee
    •  & Ingo Wohlgemuth

  • Article |

    Cryo-electron microscopy structures of the noradrenaline transporter (NET) reveal binding modes of adrenaline, coordination of sodium and chloride ion binding and the binding sites and mechanisms of inhibition by conotoxin, bupropion and ziprasidone.

    • Tuo Hu
    • , Zhuoya Yu
    •  & Yan Zhao

  • Article |

    Cryogenic electron microscopy structures of Mycobacterium tuberculosis ATP synthase and human ATP synthase bound to the anti-tuberculosis drug bedaquiline or its analogue TBAJ-587 shed light on drug binding and could lead to new treatments for tuberculosis.

    • Yuying Zhang
    • , Yuezheng Lai
    •  & Hongri Gong

  • Article |

    Radiopharmaceuticals engineered with click chemistry to selectively bind to tumour-specific proteins can be used to successfully target tumour cells, boosting the pharmacokinetics of radionuclide therapy and improving tumour regression.

    • Xi-Yang Cui
    • , Zhu Li
    •  & Zhibo Liu

  • News & Views |

    The Chilean soapbark tree is the source of QS-21 — a valuable but hard-to-obtain vaccine additive. Yeast strains engineered to express all components of the QS-21 biosynthetic pathway provide an alternative route to this therapeutic.

    • Ryan Nett

  • Research Briefing |

    A hallucinogenic compound secreted by toads has served as a springboard for research into the therapeutic benefits of psychedelics. The findings suggest that these compounds exert antidepressant effects in part by binding an under-appreciated target in the brain.

  • Article |

    A completely genetically encoded boronic-acid-containing designer enzyme was created and characterized using X-ray crystallography, high-resolution mass spectrometry and 11B NMR spectroscopy, allowing chemistry that is unknown in nature and currently not possible with small-molecule catalysts.

    • Lars Longwitz
    • , Reuben B. Leveson-Gower
    •  & Gerard Roelfes

  • Article |

    Detailed analyses of the serotonin receptor 5-HT1A and the psychedelic 5-methoxy-N,N-dimethyltryptamine reveal the differences in receptor structural pharmacology that mediate signalling specificity, efficacy and potency, findings that may facilitate the development of new neuropsychiatric therapeutics.

    • Audrey L. Warren
    • , David Lankri
    •  & Daniel Wacker

  • Research Briefing |

    A broadly applicable method allows selective, rapid and efficient chemical modification of the side chain of tryptophan amino acids in proteins. This platform enables systematic, proteome-wide identification of tryptophan residues, which can form a bond (called cation–π interaction) with positively charged molecules. Such interactions are key in many biochemical processes, including protein-mediated phase separation.

  • Article |

    VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

    • Kristen A. Baltgalvis
    • , Kelsey N. Lamb
    •  & Todd M. Kinsella

  • Article |

    Monoamines and neurotoxicants share a binding pocket in VMAT1 featuring polar sites for specificity and a wrist-and-fist shape for versatility, and monoamine enrichment in storage vesicles arises from dominant import via favoured lumenal-open transition of VMAT1 and protonation-precluded binding during its cytoplasmic-open transition.

    • Jin Ye
    • , Huaping Chen
    •  & Weikai Li

  • News & Views |

    In experiments dubbed the Random Genome Project, researchers have integrated DNA strands with random sequences into yeast and mouse cells to find the default transcriptional state of their genomes.

    • Sean R. Eddy

  • Article |

    Global profiling of hyper-reactive tryptophan sites across whole proteomes using tryptophan chemical ligation by cyclization (Trp-CLiC) reveals a systematic map of tryptophan residues that participate in cation–π interactions, including functional sites that can regulate protein-mediated phase-separation processes.

    • Xiao Xie
    • , Patrick J. Moon
    •  & Christopher J. Chang

  • Article
    | Open Access

    A multidimensional proteomics analysis of the interactions between around 2,000 nuclear proteins and over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states provides insights into how chromatin states are decoded by chromatin readers.

    • Saulius Lukauskas
    • , Andrey Tvardovskiy
    •  & Till Bartke

  • Article
    | Open Access

    Studies using genetic screening, biophysical characterization and structural reconstitution elucidate the mechanism of action and enable rational design of a new class of functional compounds that glue target proteins to E3 ligases via intramolecularly bridging two domains to enhance intrinsic protein–protein interactions and promote target ubiquitination and degradation.

    • Oliver Hsia
    • , Matthias Hinterndorfer
    •  & Alessio Ciulli

  • Research Briefing |

    Public repositories of metabolomics data are expanding rapidly and can be leveraged to uncover previously undescribed metabolites. Reverse metabolomics is a workflow in which thousands of small compounds are synthesized using combinatorial chemistry, and their molecular ‘fingerprints’ are then used to discover where they are localized in tissues and biological fluids and how they are associated with health and disease in humans.

  • Article
    | Open Access

    tRNA display enables the direct selection of orthogonal aminoacyl-tRNA synthetases that acylate orthogonal tRNAs with non-canonical monomers, enabling in vivo synthesis of proteins that include these monomers and expanding the repertoire of the genetic code.

    • Daniel L. Dunkelmann
    • , Carlos Piedrafita
    •  & Jason W. Chin

  • Article
    | Open Access

    A mechanism of lipid transport inhibition has been identified for a class of peptide antibiotics effective against resistant Acinetobacter strains, which may have applications in the inhibition of other Gram-negative pathogens.

    • Karanbir S. Pahil
    • , Morgan S. A. Gilman
    •  & Daniel Kahne

  • Article |

    Enzyme-bound ketyl radicals derived from thiamine diphosphate are selectively generated through single-electron oxidation by a photoexcited organic dye and shown to lead to enantioselective radical acylation reactions.

    • Yuanyuan Xu
    • , Hongwei Chen
    •  & Xiaoqiang Huang

  • Article
    | Open Access

    A new discovery strategy, ‘reverse metabolomics’, facilitates high-throughput matching of mass spectrometry spectra in public untargeted metabolomics datasets, and a proof-of-concept experiment identified an association between microbial bile amidates and inflammatory bowel disease.

    • Emily C. Gentry
    • , Stephanie L. Collins
    •  & Pieter C. Dorrestein

  • Article |

    Cellular lysine residues can be both methylated and acetylated on the same sidechain to form Nε-acetyl-Nε-methyllysine (Kacme), which is found on histone H4 across a range of species and across mammalian tissues and is associated with active chromatin.

    • William J. Lu-Culligan
    • , Leah J. Connor
    •  & Matthew D. Simon

  • Article |

    A scalable total synthesis of portimines enables structural reassignment of portimine B and in-depth functional evaluation of portimine A, revealing that portimine A induces translation inhibition selectively in human cancer cells and is efficacious in vivo tumour-clearance models.

    • Junchen Tang
    • , Weichao Li
    •  & Phil S. Baran

  • News & Views |

    Molecules have been developed that switch a transcription factor from being a repressor of gene expression to an activator — and thereby able to kill cancer cells. The findings offer a fresh strategy for designing anticancer drugs.

    • James D. Phelan
    •  & Louis M. Staudt

  • Article |

    A biosensor comprising bacteria engineered to respond to transient inflammatory signals has been packaged with electronic readout and transmission circuits in a small device that could be swallowed to monitor gastrointestinal health.

    • M. E. Inda-Webb
    • , M. Jimenez
    •  & T. K. Lu

  • Article |

    A new class of molecules can recruit downstream transcription factors or endogenous cancer drivers to cell death promoters and activate the expression of these genes.

    • Sai Gourisankar
    • , Andrey Krokhotin
    •  & Gerald R. Crabtree

  • Article |

    X-ray crystallography and cryo-electron microscopy analyses of Lettuce—a DNA mimic of GFP—bound to various fluorophores reveal previously unknown structures of DNA that rival analogous RNAs in complexity.

    • Luiz F. M. Passalacqua
    • , Michael T. Banco
    •  & Adrian R. Ferré-D’Amaré

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