Volume 10 Issue 4, April 2018

Volume 10 Issue 4

Fitting foldamers through the ribosome

The fabrication of foldamer–peptide hybrids offers the opportunity to create molecules with properties that are not exhibited by natural peptides. Now, a team led by Hiroaki Suga and Ivan Huc have shown that it is possible to attach a foldamer to the N-terminus of a peptide that can subsequently be extended by ribosomal synthesis. The foldamer must be unfolded to pass through the ribosome exit tunnel, but once it has emerged it can re-fold and also influence the folding of the peptide chain. The image on the cover shows one foldamer–peptide hybrid passing through the ribosome along with others that have regained their folded conformation after emerging from it.

See Rogers et al.

Image: Joseph Rogers, University of Tokyo. Cover Design: Tulsi Voralia

Thesis

  • Thesis |

    To appreciate women’s contribution to science, Michelle Francl suggests it’s time to stop talking about the most famous one.

    • Michelle Francl

News & Views

  • News & Views |

    The aqueous hydronium cation diffuses about twice as fast as the aqueous hydroxide anion in liquid water, but the origin of this behaviour has been unclear. Now, state-of-the-art simulations provide an explanation for this long-standing conundrum.

    • Ji Chen
    •  & Angelos Michaelides
  • News & Views |

    Ribosomes have now been shown to accept certain initiator tRNAs acylated with aromatic foldamer–dipeptides thereby enabling the translation of a peptide or protein with a short aromatic foldamer at the N-terminus. Some foldamer–peptide hybrids could be cyclized to generate macrocycles that present conformationally restricted peptide loops.

    • Alanna Schepartz
  • News & Views |

    Evolution of highly functionalized DNA could enable the discovery of artificial nucleic acid sequences with different properties to natural DNA. Now, an artificial translation system has been designed that can support the evolution of non-natural sequence-defined nucleic acid polymers carrying eight different functional groups on 32 codons.

    • John C. Chaput

Perspectives

  • Perspective |

    Organic synthesis is a rate-limiting factor in drug discovery, so the pharmaceutical industry heavily relies on academic research. This Perspective highlights some of the most pressing challenges to be overcome from the industrial viewpoint — such as the development of reactions tolerating specific functionalities — and encourages stronger industry–academia relationships. Credit: Pills image: Profimedia.CZ a.s. / Alamy Stock Photo; Factory image: Diana Johanna Velasquez / Alamy Stock Vector; Graduate hat: Michael Burrell / Alamy Stock Photo; Conical flask: Astex.

    • David C. Blakemore
    • , Luis Castro
    • , Ian Churcher
    • , David C. Rees
    • , Andrew W. Thomas
    • , David M. Wilson
    •  & Anthony Wood

Review Articles

  • Review Article |

    Phytochemicals exhibit great pharmaceutical importance despite their low abundance in nature. The microbial biosynthesis of complex phytochemicals offers one route to increase their availability and production. This Review discusses recent strategies to reconstruct plant biosynthetic pathways that have not been fully elucidated; enhance plant enzyme activity; and enhance overall reaction efficiency of multi-enzyme pathways.

    • Sijin Li
    • , Yanran Li
    •  & Christina D. Smolke

Articles

  • Article |

    The extent to which peptide synthesis by the ribosome can tolerate the inclusion of non-peptidic components is not clear. Yet such hybrids would expand the range of ribosomally synthesized structures. Now it has been shown that tRNAs acylated by aromatic foldamers can initiate the ribosomal synthesis of non-cyclic and cyclic foldamer–peptide hybrid molecules. The oligo-aryl segments contain folding information that can control peptide conformation in the hybrids.

    • Joseph M. Rogers
    • , Sunbum Kwon
    • , Simon J. Dawson
    • , Pradeep K. Mandal
    • , Hiroaki Suga
    •  & Ivan Huc
  • Article |

    Even though the Grotthuss mechanism was proposed two centuries ago, it is still unclear why proton transfer via the hydroxide ion is slower than that via hydronium. Advanced ab initio molecular dynamics simulations now show that it is because proton transfer via hydroxide is less temporally correlated than transfer via hydronium.

    • Mohan Chen
    • , Lixin Zheng
    • , Biswajit Santra
    • , Hsin-Yu Ko
    • , Robert A. DiStasio Jr
    • , Michael L. Klein
    • , Roberto Car
    •  & Xifan Wu
  • Article |

    A method to produce sequence-defined, diversely functionalized nucleic acid polymers that bind to proteins of biomedical interest has been developed. The method is based on a ligase-mediated, DNA-templated polymerization system and in vitro selection. The selected polymers are shown to bind their targets in a manner that is strongly dependent on specific side chains at certain polymer positions.

    • Zhen Chen
    • , Phillip A. Lichtor
    • , Adrian P. Berliner
    • , Jonathan C. Chen
    •  & David R. Liu
  • Article |

    Halogen bonding is known to get stronger with increasing halogen polarizability, but some trends of the periodic table break down for heavy elements owing to relativistic effects. Now, through distribution coefficient measurements and relativistic quantum mechanical calculations, AtI has been shown to form stronger halogen bonds than I2—meaning that astatine conforms to the trend.

    • Ning Guo
    • , Rémi Maurice
    • , David Teze
    • , Jérôme Graton
    • , Julie Champion
    • , Gilles Montavon
    •  & Nicolas Galland
  • Article |

    Calculations at the theoretical gold standard generally yield accurate results for a variety of energy-transfer processes in molecular collisions. Using anti-seeding methods in a crossed-beam inelastic scattering experiment, a resonance structure is clearly resolved for NO–H2 collisions, pushing the required accuracy for theoretical potentials beyond the gold standard.

    • Sjoerd N. Vogels
    • , Tijs Karman
    • , Jacek Kłos
    • , Matthieu Besemer
    • , Jolijn Onvlee
    • , Ad van der Avoird
    • , Gerrit C. Groenenboom
    •  & Sebastiaan Y. T. van de Meerakker
  • Article |

    Encoded display of multiple chemical elements on a constant macrocyclic scaffold could mimick antibody–antigen recognition. A chemical library constructed using this approach enabled the identification of specific binders against a variety of protein targets, including difficult targets, such as TNF.

    • Yizhou Li
    • , Roberto De Luca
    • , Samuele Cazzamalli
    • , Francesca Pretto
    • , Davor Bajic
    • , Jörg Scheuermann
    •  & Dario Neri
  • Article |

    Isotope effects provide deep insight into mechanisms of chemical and biochemical processes. Now, it has been shown that the pattern of isotopic substitution of the isomerizing bond of the retinal chromophore in the visual pigment rhodopsin significantly alters the reaction quantum yield—revealing a vibrational phase-dependent isotope effect.

    • C. Schnedermann
    • , X. Yang
    • , M. Liebel
    • , K. M. Spillane
    • , J. Lugtenburg
    • , I. Fernández
    • , A. Valentini
    • , I. Schapiro
    • , M. Olivucci
    • , P. Kukura
    •  & R. A. Mathies
  • Article |

    Heterometallic nanomaterials in unusual crystal phases that are impossible to form in the bulk state can show interesting physical and chemical properties. Here, crystal-phase heterostructured 4H/fcc Au nanowires are used as seeds to epitaxially grow a variety of binary and ternary hybrid noble metal nanostructures on the phase boundary.

    • Qipeng Lu
    • , An-Liang Wang
    • , Yue Gong
    • , Wei Hao
    • , Hongfei Cheng
    • , Junze Chen
    • , Bing Li
    • , Nailiang Yang
    • , Wenxin Niu
    • , Jie Wang
    • , Yifu Yu
    • , Xiao Zhang
    • , Ye Chen
    • , Zhanxi Fan
    • , Xue-Jun Wu
    • , Jinping Chen
    • , Jun Luo
    • , Shuzhou Li
    • , Lin Gu
    •  & Hua Zhang
  • Article |

    Nearly all organic carbon has now been quantified and characterized in a highly complex evolving atmospheric system, specifically, the multigenerational oxidation of α-pinene. It has been observed that initial addition of functional groups quickly gives way to fragmentation reactions, with organic carbon ultimately becoming sequestered in chemically resistant reservoirs: organic aerosols and long-lived gas-phase species.

    • Gabriel Isaacman-VanWertz
    • , Paola Massoli
    • , Rachel O’Brien
    • , Christopher Lim
    • , Jonathan P. Franklin
    • , Joshua A. Moss
    • , James F. Hunter
    • , John B. Nowak
    • , Manjula R. Canagaratna
    • , Pawel K. Misztal
    • , Caleb Arata
    • , Joseph R. Roscioli
    • , Scott T. Herndon
    • , Timothy B. Onasch
    • , Andrew T. Lambe
    • , John T. Jayne
    • , Luping Su
    • , Daniel A. Knopf
    • , Allen H. Goldstein
    • , Douglas R. Worsnop
    •  & Jesse H. Kroll
  • Article |

    Collisions between atoms and molecules are largely understood; however, our understanding of collisions between two molecules is lacking because they are significantly harder to study, Now, correlated rotational excitations have been observed in inelastic collisions between NO and O2 molecules. It is shown that the energy-gap law that governs atom–molecule collisions does not generally apply to bimolecular excitation processes.

    • Zhi Gao
    • , Tijs Karman
    • , Sjoerd N. Vogels
    • , Matthieu Besemer
    • , Ad van der Avoird
    • , Gerrit C. Groenenboom
    •  & Sebastiaan Y. T. van de Meerakker
  • Article |

    The construction of dynamic protein–DNA nano-assemblies suitable for modulating protein proximities and activities has now been demonstrated. This approach uses DNA strand displacement and can enable control of enzyme activity to be programmed using logic gates. As a demonstration, a split enzyme capable of activating a prodrug is triggered is by cancer-specific miRNAs.

    • Rebecca P. Chen
    • , Daniel Blackstock
    • , Qing Sun
    •  & Wilfred Chen

In Your Element

  • In Your Element |

    From its scarcity to political intrigue over naming conventions, element 108’s story describes how international cooperation overcame the limits of nuclear science, says Michael Tarselli.

    • Michael A. Tarselli