Chemical biology

  • Article |

    The transport of anions across bilayer membranes is achieved by ion channel proteins, but some small molecules are also able to mediate transmembrane movement of anions. In this study, the halogen bonding of small perfluorinated molecules is shown to allow the transmembrane movement of anions.

    • Andreas Vargas Jentzsch
    • , Daniel Emery
    •  & Stefan Matile
  • Article |

    InArabidopsis the photoperiod pathway promotes flowering in response to longer days, but during short days flowering depends on gibberellin accumulation. This study shows that TEMPRANILLO downregulation is required to induce flowering, as TEMPRANILLOgenes repress floral induction in the photoperiod and gibberellin pathways.

    • Michela Osnato
    • , Cristina Castillejo
    •  & Soraya Pelaz
  • Article
    | Open Access

    Phage display screening can unravel protein–protein interactions, but its application has been mainly restricted to the cell surface. Here, a phage-based reagent is introduced that allows the targeting of combinatorial peptides to cell organelles, providing a tool for the discovery of intracellular ligand-receptors.

    • Roberto Rangel
    • , Liliana Guzman-Rojas
    •  & Wadih Arap
  • Article
    | Open Access

    The pentameric ligand gated ion channel fromErwinia chrysanthemi(ELIC) is similar in structure to the nicotinic acetylcholine receptor, a member of the Cys-loop receptor family. This study reports the crystal structure of ELIC bound to acetylcholine and shows that acetylcholine is a competitive antagonist of ELIC.

    • Jianjun Pan
    • , Qiang Chen
    •  & Pei Tang
  • Article
    | Open Access

    β-Catenin can be oncogenic but finding inhibitors has been a challenge. Here, five compounds are identified, which attenuate transcriptional β-catenin outputs in colorectal cancer cells, and the response to one of them is shown to require an intrinsically labile α-helix next to the BCL9-binding site in β-catenin.

    • Marc de la Roche
    • , Trevor J. Rutherford
    •  & Mariann Bienz
  • Article
    | Open Access

    Algae show much promise in the production of biofuels owing to their high photoautotrophic biomass and lipid production rates. In this study, the draft genome ofNannochloropsis gaditanaCCMP526 and a method for the transformation of this alga are reported, facilitating the investigation of lipid synthesis and biofuel production.

    • Randor Radakovits
    • , Robert E. Jinkerson
    •  & Matthew C. Posewitz
  • Article
    | Open Access

    Molecular factors, regulating the expression of specific glycolytic enzymes that favour biosynthetic processes, have remained unknown. Panasyuket al. identify PPARγ as a novel transcription factor turning on pyruvate kinase M2 and hexokinase 2, which are frequently upregulated in pathophysiological growth.

    • Ganna Panasyuk
    • , Catherine Espeillac
    •  & Mario Pende
  • Article |

    Multivalent display of integrin antagonists enhances their efficacy, but current synthetic scaffolds used to display ligands are limited in range and precision. Englundet al. develop a new scaffold to study the multivalent effects of integrin antagonists across wide ranges of ligand number, density, and 3D arrangement.

    • Ethan A. Englund
    • , Deyun Wang
    •  & Daniel H. Appella
  • Article
    | Open Access

    G-protein-coupled receptors sense extracellular cues and transmit the signal to distinct trimeric G-proteins. Stefanet al.show that in response to cAMP, a central and conserved component of the Gαs-coupled receptor cascade, the RII subunit of PKA, specifically binds to and participates in Gαi signaling.

    • Eduard Stefan
    • , Mohan K. Malleshaiah
    •  & Stephen W. Michnick
  • Article
    | Open Access

    New approaches are required to combatPlasmodium falciparuminfection. In this proteome-wide study, 1305 phosphorylation sites are identified and 36 kinases are shown to have crucial roles in parasite survival, providing new insights into parasite biology and potential new drug targets for anti-malarial chemotherapy.

    • Lev Solyakov
    • , Jean Halbert
    •  & Christian Doerig
  • Article
    | Open Access

    Female Swallowtail butterflies will only lay their eggs on a small number of plants, which they choose by detecting specific chemicals on the leaf surface. Here, a gustatory receptor,PxutGr1, is identified in Papilio xuthus, which is used by the butterfly to detect synephrine when selecting a host plant.

    • Katsuhisa Ozaki
    • , Masasuke Ryuda
    •  & Hiroshi Yoshikawa
  • Article |

    Differences in the arrangement of cells is a fundamental precursor to the establishment of different organs. In this study, network theory is applied at the level of individual cells to map patterns in cell-to-cell contacts, creating a new approach to objectively characterise epithelia.

    • Luis M. Escudero
    • , Luciano da F. Costa
    •  & M. Madan Babu
  • Article |

    Large scale synapse assays can facilitate identification of drug leads. Shiet al. develop a 'synapse microarray' technology that enables sensitive, high-throughput, quantitative screening of synaptogenic events, and use it to identify novel histone deacetylase inhibitors that enhance synaptogenesis.

    • Peng Shi
    • , Mark A. Scott
    •  & Mehmet Fatih Yanik
  • Article |

    Hoop-shaped aromatic hydrocarbons can be considered as finite models of single-wall carbon nanotubes. Hitosugiet al. describe the bottom-up synthesis of a macrocyclic tetramer of chrysene, and show that its persistent rotational isomers are finite models of chiral nanotubes.

    • Shunpei Hitosugi
    • , Waka Nakanishi
    •  & Hiroyuki Isobe
  • Article |

    Molecular probes that can detect aqueous sulphides could help to elucidate their roles in biological signalling. Qianet al. develop two sulphide-selective fluorescent probes and demonstrate their ability to image free sulphide in living cells.

    • Yong Qian
    • , Jason Karpus
    •  & Chuan He
  • Article
    | Open Access

    Advanced biofuels with comparable properties to petroleum-based fuels could be microbially produced from lignocellulosic biomass. In this study,Escherichia coliis engineered to produce bisabolene, the immediate precursor of bisabolane, a biosynthetic alternative to D2 diesel.

    • Pamela P. Peralta-Yahya
    • , Mario Ouellet
    •  & Taek Soon Lee
  • Article
    | Open Access

    Cell-penetrating peptides can deliver molecular cargoes into living cells, and cross biological membranes by transduction—a non-endocytic mechanism. Here, the transduction efficiency of cyclic arginine-rich peptides is shown to be higher than that of more flexible linear peptides.

    • Gisela Lättig-Tünnemann
    • , Manuel Prinz
    •  & M. Cristina Cardoso
  • Article
    | Open Access

    Many mammals are born with an immature intestinal epithelium, which adapts to a changing diet during the weaning period. Muncanet al. show that the transcriptional repressor Blimp1is expressed in the intestine of mice at birth, and that expression is lost at the transition to the weaning stage.

    • Vanesa Muncan
    • , Jarom Heijmans
    •  & Gijs R. van den Brink
  • Article |

    Class I anti-arrhythmic drugs act at cardiac sodium channels and are subdivided into classes Ia-c based on their effects on the electrocardiogram. Here, class Ib drugs are found to rely on cation–pi interactions for their activity, whereas class Ib and Ic drugs rely significantly less on this interaction.

    • Stephan A. Pless
    • , Jason D. Galpin
    •  & Christopher A. Ahern
  • Article |

    Encapsulating molecules within supramolecular frameworks for potential biological application is challenging. Bhatiaet al. incorporate a fluorescent polymer within an icosahedral DNA nanocapsule, and show that it can be used to target specific cells in vivoand map pH spatially and temporally.

    • Dhiraj Bhatia
    • , Sunaina Surana
    •  & Yamuna Krishnan
  • Article
    | Open Access

    Secondary metabolites are widely used in human health and nutrition, but extraction yields from plants are often low. Nakagawaet al. have engineered the metabolism of Escherichia colito develop a fermentation system that produces plant alkaloids from simple carbon sources.

    • Akira Nakagawa
    • , Hiromichi Minami
    •  & Hidehiko Kumagai
  • Article
    | Open Access

    Duchenne muscular dystrophy is caused by a loss of thedystrophin gene, and control of dystrophin mRNA splicing could aid treatment of the disease. Nishida et al. show that a small molecule promotes skipping of exon 31 and increases production of a functional dystrophin protein in a patient.

    • Atsushi Nishida
    • , Naoyuki Kataoka
    •  & Masafumi Matsuo
  • Article
    | Open Access

    Cyanide-releasing defence systems in plants and animals are important to the evolution of plant–herbivore interactions. The authors identify the enzymes responsible for biosynthesis of cyanogenic glucosides by Six-spot Burnet moth caterpillars, which have evolved independently from the known plant pathway.

    • Niels Bjerg Jensen
    • , Mika Zagrobelny
    •  & Søren Bak
  • Article |

    Water-soluble peptides with stable α-helical conformations are desirable for a range of applications, but incorporating charged residues to improve solubility usually leads to reduced helical stability. Here, polypeptides produced from amino acids with elongated charged side chains are found to be water soluble and exhibit very high helical stability.

    • Hua Lu
    • , Jing Wang
    •  & Jianjun Cheng
  • Article
    | Open Access

    γ-Secretase modulators have promise in the treatment of Alzheimer's disease, but their molecular target is uncertain. Here, fluorescence resonance energy transfer is used to determine that the γ-secretase allosteric site is within the γ-secretase complex and that substrate docking is required for modulators to access the site.

    • Kengo Uemura
    • , Katherine C. Farner
    •  & Oksana Berezovska
  • Article
    | Open Access

    The influenza virus life cycle relies on sialidases, which are classified as group-1 or group-2, depending on the flexibility of the '150-loop'. In this study, chemical compounds are developed, which lock open the '150-loop', selectively inhibiting the activity of group-1 sialidases.

    • Santosh Rudrawar
    • , Jeffrey C. Dyason
    •  & Mark von Itzstein
  • Article
    | Open Access

    Frataxin is an essential protein that has been linked to iron–sulphur cluster assembly, and reduced levels are associated with Friedrich's ataxia. In this study, a combination of techniques is used to probe the interactions of the bacterial frataxin orthologue CyaY with the iron–sulphur cluster assembly machinery.

    • Filippo Prischi
    • , Petr V. Konarev
    •  & Annalisa Pastore
  • Article |

    The kinase Dyrk1A is essential for brain function and development, and its excessive activity has been implicated in Down syndrome. In this study, a selective inhibitor of Dyrk1A is developed, which may help to elucidate the molecular mechanisms of normal and diseased brain.

    • Yasushi Ogawa
    • , Yosuke Nonaka
    •  & Masatoshi Hagiwara
  • Article |

    NMDA receptors are complexes of NR1 and NR2 subunits that mediate excitatory synaptic transmission and have roles in neurological disorders. Here, a subunit-selective potentiator of NMDA receptors is identified, which may allow the evaluation of the functional roles of individual NMDA receptor subunits.

    • Praseeda Mullasseril
    • , Kasper B. Hansen
    •  & Stephen F. Traynelis
  • Review Article |

    Biologically active molecules can be identified through the screening of small-molecule libraries, but compound collections typically consist of large numbers of structurally similar compounds. Gallowayet al. review how diversity-oriented synthesis can efficiently generate structurally diverse compound libraries.

    • Warren R.J.D. Galloway
    • , Albert Isidro-Llobet
    •  & David R. Spring
  • Article |

    A crucial transition in the origin of life was the emergence of self-replicating RNA and its compartmentalization within protocellular structures. Here it is shown that the physicochemical properties of ice, a simple medium widespread on a temperate early earth, could have mediated this transition.

    • James Attwater
    • , Aniela Wochner
    •  & Philipp Holliger
  • Article
    | Open Access

    Candidate anti-tuberculosis drugs are often identified in whole-cell screens. Here, Petheet al. show that inappropriate carbon-source selection can lead to the identification of compounds devoid of efficacy in vivo, underlining the importance of developing predictive in vitroscreens.

    • Kevin Pethe
    • , Patricia C. Sequeira
    •  & Thomas Dick
  • Article |

    Electrons in metals at extremely high magnetic fields show interesting quantum structures. The authors measure the angle-dependent Nernst effect with high precision and show that, for bismuth, Coulomb interactions between the electrons become important in this ultraquantum regime.

    • Huan Yang
    • , Benoît Fauqué
    •  & Kamran Behnia