Chemical biology articles within Nature Chemical Biology

Featured

  • Research Briefing |

    We developed a rational approach to design peptide-based covalent inhibitors and coupled the inhibitors with antibodies for cell-specific delivery. We used this platform to generate antibody–peptide inhibitor conjugates (APICs) that target a family of proteases, the cysteine cathepsins. Our drug design and targeted delivery approach ensure specific inhibition and achieve therapeutic efficacy in different cancer cells and osteoclasts.

  • Article
    | Open Access

    Huang et al. report the tertiary structure of a small monomeric fluorogenic RNA aptamer named Clivia, characterized by a large Stokes shift, revealing the fluorescence activation mechanism and enabling a multivalent design to enhance the fluorescence output at specific dye concentrations.

    • Kaiyi Huang
    • , Qianqian Song
    •  & Aiming Ren

  • Article |

    Cathepsins are relevant therapeutic targets in cancer and other diseases. Here, the authors developed a different approach to block the activity of cathepsins in specific cellular contexts by combining non-natural peptide inhibitors with antibodies, enhancing therapeutic efficacy while reducing side effects.

    • Aaron Petruzzella
    • , Marine Bruand
    •  & Elisa Oricchio

  • News & Views |

    The ZDHHC family of palmitoyl transferases lipidates numerous protein targets, but the paucity of selective inhibitors has hindered their target profiling. A generalized chemical genetic system can now map the protein targets of individual ZDHHC family members.

    • Tong Lan
    •  & Bryan C. Dickinson

  • News & Views |

    Targeted protein degradation has emerged as a promising approach in drug discovery, harnessing a cell’s intrinsic machinery to eliminate disease-related proteins. Now, a study paves the way to translating this technology into potential anti-mycobacterial therapies, by exploiting the bacterial protein-degradation complex.

    • Delia Preti
    • , Valentina Albanese
    •  & Peggy Carla Raffaella Marconi

  • Article |

    Engineered living materials harness the computational power of biology to control interesting material properties. Here the authors leverage complex transcriptional regulation of bacterial extracellular electron transfer to control hydrogel cross-linking with Boolean logic.

    • Austin J. Graham
    • , Gina Partipilo
    •  & Benjamin K. Keitz

  • News & Views |

    Reliably identifying ubiquitin ligase interactors and substrates has been a persistent challenge in cellular biology. A breakthrough comes in the form of a potent, selective and cell-active chemical probe, shedding light on the intricate functions of a key regulatory enzyme.

    • Shaoshuai Xie
    •  & Gang Li

  • Article |

    Owens et al. reported PFI-7, a selective and potent antagonist of GID4 of the CTLH E3 ligase complex, which enables identification of human GID4 targets. This study provides valuable insights into GID4 functions and a powerful tool for advancing new targeted protein degradation strategies.

    • Dominic D. G. Owens
    • , Matthew E. R. Maitland
    •  & Cheryl H. Arrowsmith

  • Article |

    A newly developed maternally selective nanobody antagonist against the angiotensin II type I receptor stabilizes the receptor in a hybrid conformation and simultaneously binds with specific small-molecule antagonists.

    • Meredith A. Skiba
    • , Sarah M. Sterling
    •  & Andrew C. Kruse

  • News & Views |

    Ferroptosis, a cell death mechanism induced by lipid peroxidation, is pivotal in tumor suppression. A recent study shows that tumor repopulating cells evade ferroptosis and develop resistance to therapy via subverting a lipid metabolism enzyme.

    • Yuelong Yan
    •  & Boyi Gan

  • Review Article |

    CRISPR–Cas13 systems use single-subunit RNA-guided Cas13 effectors for targeted RNA recognition and cleavage. This Review summarizes the recent advances in understanding the structural and mechanistic aspects of Cas13 systems and the diverse applications of these systems in biotechnology and therapeutics.

    • Hui Yang
    •  & Dinshaw J. Patel

  • News & Views |

    Understanding the role of pyrophosphorylation requires specific analytical strategies to discriminate it from protein phosphorylation. A custom workflow reveals that nucleolar protein pyrophosphorylation in human cells regulates the transcription of ribosomal DNA.

    • Claire E. Eyers
    •  & Christopher J. Clarke

  • Article
    | Open Access

    A tailored proteomics workflow to identify endogenous protein pyrophosphorylation in human cells was developed, revealing the dependence of the modification on inositol pyrophosphates and a putative function in rDNA transcription.

    • Jeremy A. M. Morgan
    • , Arpita Singh
    •  & Dorothea Fiedler

  • Article |

    Cryo-electron microscopy (cryo-EM), kinetic analysis and single-molecule biochemistry reveal how the tubulin tyrosine ligase-like 6 (TTLL6) glutamylase binds reads microtubule geometry and modification state of neighboring tubulins, enabling a spatial positive feedback loop for microtubule modification.

    • Kishore K. Mahalingan
    • , Danielle A. Grotjahn
    •  & Antonina Roll-Mecak

  • News & Views |

    Reprogramming intercellular mechanotransduction and signaling pathways is still challenging. A recent advance uses a plug-and-play DNA nanodevice to allow non-mechanosensitive receptor tyrosine kinase (RTK) to transmit force-induced cellular signals.

    • Ahsan Ausaf Ali
    • , Mahmoud Amouzadeh Tabrizi
    •  & Mingxu You

  • Article
    | Open Access

    Developing disease-modifying drugs for neurodegenerative diseases has been very challenging. Now a machine learning approach has been used to identify small molecule inhibitors of α-synuclein aggregation, a process implicated in Parkinson’s disease and other synucleinopathies. Compounds that bind to the catalytic sites on the surface of the aggregates were identified and then progressively optimized into secondary nucleation inhibitors.

    • Robert I. Horne
    • , Ewa A. Andrzejewska
    •  & Michele Vendruscolo

  • Meeting Report |

    Chemical approaches, such as those that leverage induced proximity, targeted degradation, synthetic gene regulators or protein design offer opportunities to therapeutically target cellular processes that have long been thought of as undruggable. We report on the progress and the potential for transformative collaborations between fields discussed at the 2023 Bringing Chemistry to Medicine symposium at St. Jude Children’s Research Hospital.

    • Caitlin D. Deane
    • , Marcus Fischer
    •  & Anang A. Shelat

  • News & Views |

    Peptide vaccines use antigenic peptide fragments to induce an immune response but are problematic because of the short half-life of peptides. A study now reports thioamide substitution in the peptide backbone as a strategy to enhance resistance to proteolysis and promote binding to the MHC I complex for T cell activation.

    • Martin Zacharias
    •  & Sebastian Springer

  • News & Views |

    Detection of intracellular lipolysaccharide (LPS) activates an immune response initiated by the non-canonical inflammasome. ATGL has now been identified as a negative regulator of this pathway that dampens inflammation by removing LPS’ acyl chains, preventing the activation of inflammatory caspases and cytokines.

    • Gemma Banister
    •  & Dave Boucher

  • News & Views |

    Chemogenetic profiling can reveal genetic determinants that coordinate phenotypic responses to therapeutics, along with predicting potential pathways of resistance. A new analytical method for evaluating chemogenetic profiles reveals contributions from death-regulatory genes.

    • Jesse D. Gelles
    •  & Jerry Edward Chipuk

  • Article |

    A proteomics and computational approach was developed to map the proximal proteome of the activated μ-opioid receptor and to extract subcellular location, trafficking and functional partners of G-protein-coupled receptor activity.

    • Benjamin J. Polacco
    • , Braden T. Lobingier
    •  & Ruth Hüttenhain

  • News & Views |

    BURP-domain proteins belong to an emerging class of autocatalytic copper-containing proteins that modify themselves after synthesis. Now, a report explains how their structure and metal coordination sphere control the installation of crosslinks within the core peptide, and shows how nature leverages mechanistic paradigms to create diversity.

    • Ninian J. Blackburn

  • Article |

    Huang et al. developed E3-substrate tagging by ubiquitin biotinylation (E-STUB), a proximity labeling-based method for direct identification of ubiquitylated substrates for a given E3 ligase, providing a useful tool for substrate discovery of targeted protein degradation and the understanding of E3 ligase function.

    • Hai-Tsang Huang
    • , Ryan J. Lumpkin
    •  & William R. Sellers

  • Article |

    Hypoxia induces ·NO-dependent hydrogen sulfide (H2S) biogenesis by inhibiting the transsulfuration pathway. H2S oxidation promotes endothelial cell proliferation to support neovascularization in tissue injury and tumor xenograft models.

    • Roshan Kumar
    • , Victor Vitvitsky
    •  & Ruma Banerjee

  • News & Views |

    An integrative approach has now enabled elucidation of the complete biosynthetic pathway of a prominent saponin adjuvant. Reconstruction of the whole biosynthetic pathway in a heterologous host provides new perspectives for the biotechnological supply of this immunostimulant.

    • Vincent Courdavault
    •  & Nicolas Papon

  • Article
    | Open Access

    The study demonstrates that specific recognition and custom binding geometries can be computationally encoded between protein spans within lipids through designing synthetic transmembrane proteins to functionally regulate a target cytokine receptor.

    • Marco Mravic
    • , Li He
    •  & William F. DeGrado

  • News & Views |

    Reprogramming of the genetic code allows the synthesis of proteins using new building blocks, thus opening the door to the development of a wider variety of medicines and biocatalysts; however, it is currently limited to α-amino acids. A new study has now reported the incorporation of β-linked and α,α-disubstituted monomers into a ribosome-synthesized protein.

    • Ya-Ming Hou
    •  & Yuko Nakano

  • Comment |

    AlphaFold is a breakthrough in protein structure prediction, but limitations in its application to computation- and structure-guided drug discovery remain. As with structure prediction, public-domain data and benchmarking initiatives will be essential to advance the field of computational drug design.

    • Matthieu Schapira
    • , Levon Halabelian
    •  & Rachel J. Harding

  • News & Views |

    Kir4.1 potassium channels expressed in astroglial cells critically regulate extracellular potassium concentration in the brain. A new study reports that blocking the flow of potassium ions into astrocytes by inhibiting Kir4.1 induces rapid-onset antidepressive effects in rodents.

    • Jerod S. Denton

  • News & Views |

    Labeling of endogenous proteins with chemical probes is highly desirable for life science studies. The combination of RNA base editing and site-specific incorporation of non-canonical amino acids allows the introduction of small chemical tags into endogenous proteins in living cells.

    • Tomohiro Doura
    • , Yuma Matsuoka
    •  & Shigeki Kiyonaka

  • Article |

    Aerobic glycolysis is a hallmark of fast-growing cells, but it is unclear whether glycolysis was selected for its speed. Glycolysis produces ATP slower than respiration (per protein mass) and is beneficial for rendering cells robust to hypoxia.

    • Yihui Shen
    • , Hoang V. Dinh
    •  & Joshua D. Rabinowitz

  • News & Views |

    Inhibitors of KRAS G12C have shown that directly targeting RAS is possible, but G12C is only one of many RAS driver mutations. Covalent targeting of another major variant, G12D, raises hope for treating other groups of patients with KRAS-mutant tumors.

    • Kenneth Westover

Browse broader subjects

Browse narrower subjects

Browse Chemical biology across other nature.com journals