Volume 5 Issue 3, March 2013

Volume 5 Issue 3

Robin Hochstrasser and colleagues have used vibrational spectroscopy, X-ray crystallography and simulations to study the role of water in the binding of the anti-AIDS drug rilpivirine to HIV-1 reverse transcriptase. The cover shows a snapshot (taken from molecular dynamics simulations) of rilpivirine within the binding pocket; the carbon, nitrogen, oxygen and hydrogen atoms are shown in cyan, blue, red and white, respectively, and the green surface represents the protein and other associated water molecules. The purple atoms are the nitrogens of the nitrile groups that are used as infrared probes.Article p174;News & Views p152IMAGE: DANIEL G. KURODACOVER DESIGN: ALEX WING


  • Thesis |

    Michelle Francl argues we should embrace molecular models, not tuck them away in the closet.

    • Michelle Francl

Books and Arts

Research Highlights


News and Views

  • News & Views |

    Overcoming drug resistance requires drug–protein interactions that persist in spite of mutations, but such interactions are difficult to characterize. Two-dimensional infrared spectroscopy can reveal the dynamics of how key molecular groups interact, allowing new insights into how some drugs overcome resistance.

    • Christopher M. Cheatum
  • News & Views |

    The direct observation and quantification of G-quadruplex structures formed from DNA in human cells during the cell cycle demonstrate the biological importance of these structures and point towards opportunities for targeting them with small-molecule drugs.

    • Adam Siddiqui-Jain
    •  & Laurence H. Hurley
  • News & Views |

    Many of us eat mushrooms, but few of us have probably ever thought about — let alone witnessed — the epic battle of kingdoms that can occur between this delicacy and its bacterial pathogens. Now, imaging mass spectrometry has enabled the identification of a bacterium's potent antifungal weapon of choice.

    • Laura M. Sanchez
    •  & Pieter C. Dorrestein
  • News & Views |

    A synthetic strategy that uses a series of simple reactions to distort the core architecture of complex natural products could provide libraries of stereochemically rich compounds that will help in the search for new biological probes and drugs.

    • Indrajeet Sharma
    •  & Derek S. Tan
  • News & Views |

    Metallic nanoparticles enable the control of optical fields at the nanometre scale, enhancing the absorption and emission of local emitters. Now, using the self-assembling properties of DNA, functional nanoantennas have been developed that comprise a versatile and robust assembly of gold nanoparticles and emitters.

    • Gonzalo Cosa


  • Review Article |

    α-Helix-mediated protein–protein interactions (PPIs) play a key role in the development of numerous infection and disease states. Modulating such interactions offers considerable therapeutic potential, however, identifying suitable inhibitors has proved challenging. This Review highlights recent and generic approaches for designing inhibitors of helix-mediated PPIs.

    • Valeria Azzarito
    • , Kérya Long
    • , Natasha S. Murphy
    •  & Andrew J. Wilson


  • Article |

    Conformational changes are known to occur during binding of the anti-AIDS drug rilpivirine to HIV-1 reverse transcriptase, an essential enzyme for the replication of HIV. Vibrational spectroscopy, X-ray crystallography and simulations now show that water molecules play an essential role in this binding process, which may help it retain potency despite mutations within the binding pocket.

    • Daniel G. Kuroda
    • , Joseph D. Bauman
    • , J. Reddy Challa
    • , Disha Patel
    • , Thomas Troxler
    • , Kalyan Das
    • , Eddy Arnold
    •  & Robin M. Hochstrasser
  • Article |

    A structure-specific antibody generated and employed to visualize DNA G-quadruplex structures in human cells shows that these structures are modulated during the cell cycle and can be stabilized by a small-molecule ligand. This provides substantive evidence for endogenous DNA G-quadruplex formation in mammalian cells.

    • Giulia Biffi
    • , David Tannahill
    • , John McCafferty
    •  & Shankar Balasubramanian
  • Article |

    When monolayers of π-conjugated organic semiconductors interact with metal surfaces, most remain semiconducting. In some cases, however, the metallic character of the substrate is seen to extend onto the molecules. A mechanism for this intriguing phenomenon is now suggested and new strategies for chemical surface engineering are proposed.

    • G. Heimel
    • , S. Duhm
    • , I. Salzmann
    • , A. Gerlach
    • , A. Strozecka
    • , J. Niederhausen
    • , C. Bürker
    • , T. Hosokai
    • , I. Fernandez-Torrente
    • , G. Schulze
    • , S. Winkler
    • , A. Wilke
    • , R. Schlesinger
    • , J. Frisch
    • , B. Bröker
    • , A. Vollmer
    • , B. Detlefs
    • , J. Pflaum
    • , S. Kera
    • , K. J. Franke
    • , N. Ueno
    • , J. I. Pascual
    • , F. Schreiber
    •  & N. Koch
  • Article |

    An approach for the construction of complex and diverse compound libraries is described, whereby natural products are altered through a series of ring system distortion reactions. The compounds produced have markedly different physiochemical properties from those in standard screening collections and thus could offer advantages in the search for lead molecules that can be developed into drug candidates.

    • Robert W. Huigens III
    • , Karen C. Morrison
    • , Robert W. Hicklin
    • , Timothy A. Flood Jr
    • , Michelle F. Richter
    •  & Paul J. Hergenrother
  • Article |

    Metal–organic framework (MOF) nanoparticles and their assembly into three-dimensional superstructures are attracting attention in various fields. Now, a general spray-drying method has been developed to create more complex hollow spherical MOF superstructures and entrap guest species within them, thereby providing new routes to capsules, reactors and composite materials.

    • Arnau Carné-Sánchez
    • , Inhar Imaz
    • , Mary Cano-Sarabia
    •  & Daniel Maspoch
  • Article |

    Time-resolved X-ray crystallography on photoactive yellow protein shows the existence of a short-lived, highly distorted intermediate whose reaction trajectory bifurcates along ‘bicycle-pedal’ and ‘hula-twist’ pathways. The bifurcating reaction pathways can be controlled by weakening the hydrogen bond between the chromophore and an adjacent residue, which switches off the bicycle-pedal pathway.

    • Yang Ouk Jung
    • , Jae Hyuk Lee
    • , Joonghan Kim
    • , Marius Schmidt
    • , Keith Moffat
    • , Vukica Šrajer
    •  & Hyotcherl Ihee
  • Article |

    Basic fibroblast growth factor (bFGF) is crucial for a range of diverse cellular processes, from wound healing to bone regeneration, yet is inherently unstable. This important biologic has now been covalently linked to a polymer that mimics the polysaccharide heparin to produce a conjugate that shows remarkable stability to a wide range of therapeutically and environmentally relevant stressors.

    • Thi H. Nguyen
    • , Sung-Hye Kim
    • , Caitlin G. Decker
    • , Darice Y. Wong
    • , Joseph A. Loo
    •  & Heather D. Maynard
  • Article |

    Electricity can be produced by the oxidation of hydrogen in fuel cells, but the best catalyst for this is platinum, a precious metal of low abundance. Now a molecular complex of iron, a very abundant, inexpensive metal, has been rationally designed for the oxidation of H2 at room temperature.

    • Tianbiao Liu
    • , Daniel L. DuBois
    •  & R. Morris Bullock
  • Article |

    A molecular tweezer has been shown to bind to the surface of a 14-3-3 protein through a particular lysine residue. This interaction — characterized in detail by protein crystallography and computational modelling — disrupts the protein's binding with partner proteins. These findings ascertain supramolecular chemistry as an enticing tool in chemical biology, here towards modulating protein functions.

    • David Bier
    • , Rolf Rose
    • , Kenny Bravo-Rodriguez
    • , Maria Bartel
    • , Juan Manuel Ramirez-Anguita
    • , Som Dutt
    • , Constanze Wilch
    • , Frank-Gerrit Klärner
    • , Elsa Sanchez-Garcia
    • , Thomas Schrader
    •  & Christian Ottmann
  • Article |

    Substituted allenes with axial chirality are of great utility in organic chemistry owing to their unique structure and reactivity, but synthetic methods to access them are limited. Here, a catalytic asymmetric synthesis of tetrasubstituted allenes is described that builds on the use of phase-transfer-catalysed asymmetric functionalization of 1-alkylallene-1,3-dicarboxylates.

    • Takuya Hashimoto
    • , Kazuki Sakata
    • , Fumiko Tamakuni
    • , Mark J. Dutton
    •  & Keiji Maruoka

In Your Element

  • In Your Element |

    D. Scott Wilbur points out the difficulty in studying the transient element astatine, and the need to understand its basic chemical nature to help in the development of targeted radiotherapy agents.

    • D. Scott Wilbur