Volume 4 Issue 9, September 2012

Volume 4 Issue 9

Current antiretroviral therapy (ART) can transform HIV infection from a terminal illness to a manageable chronic disease, but hidden HIV can re-ignite infection if treatment is stopped. Jerome Zack, Paul Wender and co-workers have now shown that a series of simplified — and thus synthetically accessible — analogues of the marine natural product bryostatin (one of which is shown on the cover) are able to activate latent HIV in vitro. It is hoped that this approach, in combination with ART, might ultimately lead to eradication of the infection.Article p705;News & Views p692IMAGE: BRIAN LOYCOVER DESIGN: ALEX WING

Thesis

  • Thesis |

    Michelle Francl wonders if home labs make (better) chemists.

    • Michelle Francl

Research Highlights

Blogroll

News and Views

  • News & Views |

    A series of highly active, simplified analogues of the natural product bryostatin have been prepared. They offer an improved approach for the activation of latent HIV that could, in combination with current state-of-the-art antiretroviral therapy, offer hope for eventual eradication of the infection.

    • Christian Melander
    •  & David M. Margolis
  • News & Views |

    Hydrogen bonds play a key role in defining the folding of proteins and the maintenance of their structure. A high-pressure NMR study of ubiquitin now provides unprecedented detail on the temperature and pressure dependence of its hydrogen-bond network.

    • Gerd Nielsen
    •  & Harald Schwalbe
  • News & Views |

    Molecular engineers have long relied on a single light-driven event or chemical input to induce structural changes in switching systems. By carefully designing two hydrazone-based switches, it has now been shown that a single metal-binding event can trigger a signalling cascade that results in the isomerization of two different molecules.

    • Shawn C. Burdette
  • News & Views |

    Synthetic receptors with properties resembling those of carbohydrate-binding proteins are known, but they are structurally rather complex. Elaborate structures are, however, not always required to bind carbohydrates in water — much simpler compounds can be just as effective.

    • Stefan Kubik

Perspective

  • Perspective |

    Although the molecular formula gives valuable information on the properties of isolated molecules or conjugated polymers, it fails to accurately predict their collective behaviour in the solid state. This Perspective highlights the importance of organization across multiple length scales on the optical and electronic properties of organic semiconductors, and how device performances poorly reflect the capabilities of a given material.

    • Zachary B. Henson
    • , Klaus Müllen
    •  & Guillermo C. Bazan

Articles

  • Article |

    Simplified bryostatin analogues are shown to potently induce latent HIV expression in vitro. These analogues display comparable or better potency when compared with bryostatin. Moreover, they are up to 1,000-fold more potent in inducing latent HIV expression than prostratin, the current lead preclinical candidate.

    • Brian A. DeChristopher
    • , Brian A. Loy
    • , Matthew D. Marsden
    • , Adam J. Schrier
    • , Jerome A. Zack
    •  & Paul A. Wender
  • Article |

    The pressure- and temperature-dependent changes of various hydrogen bonds within ubiquitin have been determined at very high resolution using NMR H-bond scalar couplings. The measured perturbations show a correlation with the sequence separation between donor and acceptor residues, and indicate that certain topologically crucial H-bonds are specifically stabilized.

    • Lydia Nisius
    •  & Stephan Grzesiek
  • Article |

    Selective carbohydrate binding is a difficult task, usually accomplished by proteins (lectins) or complex synthetic analogues. It has now been achieved by a remarkably simple compound, accessible in just five steps from commercially available materials. This new receptor is highly selective for all-equatorial carbohydrates, and may be used to sense glucose through changes in anthracene fluorescence.

    • Chenfeng Ke
    • , Harry Destecroix
    • , Matthew P. Crump
    •  & Anthony P. Davis
  • Article |

    The chemical modification of graphene is important for its use in many applications. Now it is shown that the reactivity of graphene towards covalent modification varies widely depending on its underlying support substrate, and that the substrate can be patterned to induce spatial control of chemical reactions in graphene.

    • Qing Hua Wang
    • , Zhong Jin
    • , Ki Kang Kim
    • , Andrew J. Hilmer
    • , Geraldine L. C. Paulus
    • , Chih-Jen Shih
    • , Moon-Ho Ham
    • , Javier D. Sanchez-Yamagishi
    • , Kenji Watanabe
    • , Takashi Taniguchi
    • , Jing Kong
    • , Pablo Jarillo-Herrero
    •  & Michael S. Strano
  • Article |

    Reactions with unstable and highly reactive zwitterionic intermediates generated in transition-metal-catalysed processes provide new opportunities for molecular constructions. Here imines, activated by chiral organocatalysts, have been employed to trap the zwitterionic intermediates to give polyfunctionalized indole and oxindole derivatives in a single step with excellent diastereoselectivity and enantioselectivity.

    • Huang Qiu
    • , Ming Li
    • , Li-Qin Jiang
    • , Feng-Ping Lv
    • , Li Zan
    • , Chang-Wei Zhai
    • , Michael P. Doyle
    •  & Wen-Hao Hu
  • Article |

    In heterogeneous catalytic processes the Arrhenius parameters are often found to be interrelated (compensation phenomenon). Using state-of-the-art experiments and density functional theory, the origin of compensation is studied. A similar dependence on the rate-limiting surface-coverage term is found for both apparent activation energy and prefactor terms, which can be translated into surface configurational entropy contributions.

    • Detre Teschner
    • , Gerard Novell-Leruth
    • , Ramzi Farra
    • , Axel Knop-Gericke
    • , Robert Schlögl
    • , László Szentmiklósi
    • , Miguel González Hevia
    • , Hary Soerijanto
    • , Reinhard Schomäcker
    • , Javier Pérez-Ramírez
    •  & Núria López
  • Article |

    The self-sorting of molecular building blocks should allow 2D surface patterns to be transcribed into 3D functional materials. Here, a non-empirical approach to the templated synthesis of supramolecular architectures on surfaces is reported, starting with a theoretical model and followed by comprehensive experimental validation, including direct evidence for functional relevance of the produced materials.

    • Edvinas Orentas
    • , Marco Lista
    • , Nai-Ti Lin
    • , Naomi Sakai
    •  & Stefan Matile
  • Article |

    A coordination cage has been prepared that self-assembles through second-order templation. Peripheral perchlorate or hexafluorophosphate template anions direct the formation of a hollow prism whose central pocket was able to bind a small anionic guest such as halide or azide, in a manner reminiscent to signal transduction in biological systems.

    • Imogen A. Riddell
    • , Maarten M. J. Smulders
    • , Jack K. Clegg
    • , Yana R. Hristova
    • , Boris Breiner
    • , John D. Thoburn
    •  & Jonathan R. Nitschke
  • Article |

    Metal cations play an important role in biological proton relays by modulating the pKa values of surrounding amino acids. This effect has now been used to induce the isomerization of two hydrazone switches using a single input. It is found that a combination of electrostatic repulsion and conformational changes are required for the proton relay to take place.

    • Debdas Ray
    • , Justin T. Foy
    • , Russell P. Hughes
    •  & Ivan Aprahamian

In Your Element

  • In Your Element |

    You would be forgiven if you thought the most important element in an organic transformation was carbon. Matthew Hartings argues that, for just over half a century in many of chemistry's most renowned organic reactions, it has actually been palladium.

    • Matthew Hartings