Volume 7 Issue 7, July 2015

Volume 7 Issue 7

The accuracy of hybridizationbased approaches for analysing nucleic acids is limited by a probe's specificity — as well as binding the intended target, closely related sequences may also be captured. Now, Juexiao Sherry Wang and David Yu Zhang have shown that simulations of binding kinetics can be used to guide the design of competitive hybridization-probe systems that are highly selective for specific single-nucleotide variants. With this approach, they have developed probes that, when combined with PCR amplification, can detect variant alleles at concentrations as low as 1% in human genomic DNA.Article p545IMAGE: CINDY THAUNGCOVER DESIGN: KAREN MOORE

Thesis

  • Thesis |

    Michelle Francl suggests that chemists should relax and not fret over ambiguous language.

    • Michelle Francl

Research Highlights

Blogroll

News and Views

  • News & Views |

    Bioorthogonal catalysis provides new ways of mediating artificial transformations in living environs. Now, researchers have developed a nanodevice whose catalytic activity can be regulated by host–guest chemistry.

    • Asier Unciti-Broceta
  • News & Views |

    Deoxygenation reactions have been used to convert biomass-derived carbohydrates into useful platform chemicals. Now, a method has been described that can selectively excise C–O bonds to produce valuable chiral synthons.

    • Andrew McNally
  • News & Views |

    An electrochemical clamp assay that enables the rapid and sensitive detection of nucleic acids containing single base mutations has now been developed. It has been shown to differentiate between cancer patient samples featuring a specific mutation, and controls from healthy donors or other cancer patients, all directly in unprocessed serum.

    • Irina A. Gorodetskaya
    •  & Alon A. Gorodetsky
  • News & Views |

    The transfer of chirality is known to occur through chemical bonds. Now, chiral biomolecules have been observed to impart some of their optical properties to a spatially separated achiral dye — with the transfer mediated by plasmon resonance from an achiral metallic nanostructure.

    • Vladimiro Mujica

Articles

  • Article |

    The use of kinetic simulations to guide the design of competitive hybridization probe systems is shown to enable high selectivity for single-nucleotide variants. Using this approach across 44 cancer mutation/wild-type sequence pairs showed between a 200- and 3,000-fold higher binding affinity than the corresponding wild-type sequence. In combination with PCR amplification this method enabled the detection of a 1% concentration of variant alleles in human genomic DNA.

    • Juexiao Sherry Wang
    •  & David Yu Zhang
  • Article |

    The rapid and selective regulation of a target protein within living cells containing closely related family members is a longstanding challenge. Now the introduction of genetically directed bioorthogonal ligand tethering (BOLT) and the demonstration of selective inhibition (iBOLT) and optical switching (photo-BOLT) of protein function in live mammalian cells addresses this challenge.

    • Yu-Hsuan Tsai
    • , Sebastian Essig
    • , John R. James
    • , Kathrin Lang
    •  & Jason W. Chin
  • Article |

    Roaming — a new and unusual reaction mechanism in gas-phase chemical transformations — is now shown to occur in solution. Following ultraviolet excitation of geminal tribromides, what initially seems to be the simple fission of a bond is in fact isomerization occurring through the roaming of molecular fragments.

    • Andrey S. Mereshchenko
    • , Evgeniia V. Butaeva
    • , Veniamin A. Borin
    • , Anna Eyzips
    •  & Alexander N. Tarnovsky
  • Article |

    The analysis of circulating cell-free nucleic acids (cfNA) in the blood of cancer patients permits the analysis of tumour mutations without requiring invasive sampling of tissue. Now, the development of an electrochemical assay that uses a collection of clamp molecules to sequester interfering cfNAs enables the accurate detection of mutated sequences in serum collected from people with lung cancer or melanoma.

    • Jagotamoy Das
    • , Ivaylo Ivanov
    • , Laura Montermini
    • , Janusz Rak
    • , Edward H. Sargent
    •  & Shana O. Kelley
  • Article |

    Biorenewable carbohydrate feedstocks can be efficiently converted into a diverse set of oxygen-functionalized chiral synthons using a combination of a tertiary silane and the catalyst B(C6F5)3. The deoxygenation mechanism involves cyclic intermediates, which provide a means of controlling chemo- and diastereoselectivity.

    • Laura L. Adduci
    • , Trandon A. Bender
    • , Jennifer A. Dabrowski
    •  & Michel R. Gagné
  • Article |

    The nature of actinide–ligand bonding is attracting attention, in particular in the context of nuclear waste separations. Structurally authenticated one-, two- and threefold uranium–arsenic bonding interactions are now reported. Computational analysis suggests the presence of polarized σ2, σ2π2, and σ2π4 in the arsenide, terminal arsinidene, and arsenido complexes, respectively.

    • Benedict M. Gardner
    • , Gábor Balázs
    • , Manfred Scheer
    • , Floriana Tuna
    • , Eric J. L. McInnes
    • , Jonathan McMaster
    • , William Lewis
    • , Alexander J. Blake
    •  & Stephen T. Liddle
  • Article |

    Surface-enhanced resonant Raman optical activity (SERROA) reveals the through-space transfer of chirality from biomolecules to achiral benzotriazole dye-conjugated nanotags. The chiroptical responses generated by the stereoisomers of ribose and tryptophan establish this as the basis for a stereoselective nanosensor platform.

    • Saeideh Ostovar pour
    • , Louise Rocks
    • , Karen Faulds
    • , Duncan Graham
    • , Václav Parchaňský
    • , Petr Bouř
    •  & Ewan W. Blanch
  • Article |

    Regulation of bioorthogonal catalysis in living systems is challenging because of the complex intracellular environment. Now, the activity of protein-sized bioorthogonal nanozymes has been regulated by binding a supramolecular cucurbit[7]uril ‘gate-keeper’ onto the monolayer surface. This arrangement enables the controlled activation of profluorophores and prodrugs inside living cells for imaging and therapeutic applications.

    • Gulen Yesilbag Tonga
    • , Youngdo Jeong
    • , Bradley Duncan
    • , Tsukasa Mizuhara
    • , Rubul Mout
    • , Riddha Das
    • , Sung Tae Kim
    • , Yi-Cheun Yeh
    • , Bo Yan
    • , Singyuk Hou
    •  & Vincent M. Rotello
  • Article |

    A chemical synthesis of (–)-jiadifenolide, a small molecule neurotrophin, has been achieved in eight steps. The route relies on a stereoselective coupling of two simple butenolides to build the entire skeleton in a single step and produce one gram of the target for broad distribution to the biomedical community.

    • Hai-Hua Lu
    • , Michael D. Martinez
    •  & Ryan A. Shenvi

In Your Element

  • In Your Element |

    Anders Lennartson ponders on the contribution of thallium to society, since its main characteristic is its toxicity.

    • Anders Lennartson

Corrigendum