Tuesday, January 15, 2013

Sequence-Specific Peptide Synthesis by an Artificial Small-Molecule Machine



Bartosz Lewandowski1,Guillaume De Bo1,John W. Ward1,Marcus Papmeyer1,Sonja Kuschel1,María J. Aldegunde2,Philipp M. E. Gramlich2,Dominik Heckmann2,Stephen M. Goldup2,Daniel M. D’Souza2,Antony E. Fernandes2,David A. Leigh1,2,*

The ribosome builds proteins by joining together amino acids in an order determined by messenger RNA. Here, we report on the design, synthesis, and operation of an artificial small-molecule machine that travels along a molecular strand, picking up amino acids that block its path, to synthesize a peptide in a sequence-specific manner. The chemical structure is based on a rotaxane, a molecular ring threaded onto a molecular axle. The ring carries a thiolate group that iteratively removes amino acids in order from the strand and transfers them to a peptide-elongation site through native chemical ligation. The synthesis is demonstrated with ~1018 molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry. 

Bio-Inspired Polymer Composite Actuator and Generator Driven by Water Gradients



  1. Robert Langer1,2,*

Combining both a rigid matrix (polypyrrole) and a dynamic network (polyol-borate), strong and flexible polymer films were developed that can exchange water with the environment to induce film expansion and contraction, resulting in rapid and continuous locomotion. The film actuator can generate contractile stress up to 27 megapascals, lift objects 380 times heavier than itself, and transport cargo 10 times heavier than itself. We have assembled a generator by associating this actuator with a piezoelectric element. Driven by water gradients, this generator outputs alternating electricity at ~0.3 hertz, with a peak voltage of ~1.0 volt. The electrical energy is stored in capacitors that could power micro- and nanoelectronic devices.

Surface functionalization

Templating Gold Surfaces with Function: A Self-Assembled Dendritic Monolayer Methodology Based on Monodisperse Polyester ScaffoldsKim Öberg †, Jarmo Ropponen †‡, Jonathan Kelly §, Peter Löwenhielm §, Mattias Berglin *, and Michael Malkoch *† 
In this paper, a dendrimer-functionalized gold surface was used to determine how different functionality presented by dendrimers (-OH or -mannose) affected E. coli  binding.
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Drug delivery

One-Pot Synthesis of Mesoporous Silica Nanocarriers with Tunable Particle Sizes and Pendent Carboxylic Groups for Cisplatin Delivery
Jinlou Gu *, Jiapeng Liu , Yongsheng Li , Wenru Zhao , and Jianlin Shi *


This paper reports might be good to keep in mind as drug delivery reference.

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Surface functionalization

Self-Assembled Monolayers of n-Alkanethiols Suppress Hydrogen Evolution and Increase the Efficiency of Rechargeable Iron Battery Electrodes
Souradip Malkhandi , Bo Yang , Aswin K. Manohar , G. K. Surya Prakash , and S. R. Narayanan http://pubs.acs.org/doi/full/10.1021/ja3095119

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This work describes the importance of surface passivation of iron.  Thiols do a good job, but could other ligands do better?

Self-assembled nanostructures

Dynamic or Nondynamic? Helical Trajectory in Hexabenzocoronene Nanotubes Biased by a Detachable Chiral Auxiliary
Wei Zhang,†,‡ Wusong Jin,§ Takanori Fukushima,*,∥ Noriyuki Ishii,⊥ and Takuzo Aida*,†,‡

The figure below speaks for itself.  The assembly of functional hexabenzocoronenes is non-dynamic contrary to expectation.  
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Carbene complexes

Gold(III)- versus Gold(I)-Induced Cyclization: Synthesis of Six-Membered Mesoionic Carbene and Acyclic (Aryl)(Heteroaryl) Carbene Complexes (pages 758–761)Gaël Ung, Dr. Michele Soleilhavoup and Prof. Guy Bertrand
Article first published online: 21 NOV 2012 | DOI: 10.1002/anie.201207961

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  Interesting gold carbene structures were synthesized here.


A Generic One-Pot Route to Acyclic Two-Coordinate Silylenes from Silicon(IV) Precursors: Synthesis and Structural Characterization of a Silylsilylene (pages 568–571)
Dr. Andrey V. Protchenko, Dr. Andrew D. Schwarz, Matthew P. Blake, Prof. Cameron Jones, Prof. Nikolas Kaltsoyannis, Prof. Philip Mountford and Prof. Simon Aldridge
Article first published online: 20 NOV 2012 | DOI: 10.1002/anie.201208554
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This is an important discovery -- while stable cyclic silylenes are known, this report describes the first stable acyclic silylene.  Molecules like this are likely going to be useful for surface functionalization of all things silicon.

Lewis Acid Catalysis

From JACS:

A Powerful Aluminium Catalyst for the Synthesis of Highly Functional Organic Carbonates

A novel aluminum complex promotes cycloaddition of CO2 and epoxides to form carbonates with exceptional catalytic efficiency and broad functional group tolerance.  Though they focus on conditions that avoid polymerization in this paper, this complex could end up being very useful for epoxide/CO2 copolymerizations in the style of Geoff Coates.

Surface Functionalization

From JACS:

Gas-Phase Azide Functionalization of Carbon

Chidsey and coworkers report a really nice study showing that carbon surfaces react with iodine azide gas to generate azide-functional surfaces that can then be subjected to azide-alkyne click reactions.

Ni Catalysis

From JACS:

Decarbonylative C–H Coupling of Azoles and Aryl Esters: Unprecedented Nickel Catalysis and Application to the Synthesis of Muscoride A

Itami and coworkers report a surprising decarbonylative C-H cross-coupling reaction catalyzed by a easy-to-make nickel catalyst.  They use this method for the synthesis of the natural product Muscoride A.  This work was highlighted in Angewandte here: 

Bottom-up surface architecture

Surface Plasmon Mediated Chemical Solution Deposition of Gold Nanoparticles on a Nanostructured Silver Surface at Room Temperature
Jingjing Qiu †, Yung-Chien Wu †, Yi-Chung Wang †, Mark H. Engelhard ‡, Lisa McElwee-White *†, and Wei David Wei *


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In this article, the authors describe synthesis of ligand-free gold nanoparticles (size is deposition time-tunable: 3-10 nm) on nano-structured silver surface via LSPR-promoted decomposition of Me-Au-PPh3.  Gold nanoparticle growth is surface-limited, indicating that the silver surface is essential and that no gold-nanoparticle autocatalysis is taking place.

Spherical Assemblies from π-Conjugated Alternating Copolymers: Toward Optoelectronic Colloidal Crystals


Taeko Adachi , Liang Tong , Junpei Kuwabara , Takaki Kanbara , Akinori Saeki §, Shu Seki §, and Yohei Yamamoto *


The authors demonstrated that polymers such as polyfluorene and polythiophene having a single monomer component hardly formed defined and discrete objects but only gave ill-defined aggregates. In contrast, alternating copolymers typically having both fluorene and thiophene components in their repeating unit self-assembled into well-shaped spheres with diameters ranging from several hundreds of nanometers to several micrometers. Such clear differences in terms of the assembling geometries derive from the rigidity and crystallinity of the polymers, where the copolymers possess large steric hindrance on their backbone that reduces planarity of the polymers and inhibits anisotropic crystal growth, leading to the formation of structurally isotropic spheres. Changing the assembling parameters can systematically control diameter and deviation of the spheres. Furthermore, photocarrier lifetimes of the spheres were markedly enhanced by more than 3 orders of magnitude.

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Visible-Light-Induced Reversible Complexation Mediated Living Radical Polymerization of Methacrylates with Organic Catalysts

From Macromolecules:

Visible-Light-Induced Reversible Complexation Mediated Living Radical Polymerization of Methacrylates with Organic Catalysts

Drug Delivery Systems

From J. Am. Chem. Soc.:

Acid-Active Cell-Penetrating Peptides for in Vivo Tumor-Targeted Drug Delivery

Cell-Material Interactions

From Nano Lett.:

Label-Free Segmentation of Co-cultured Cells on a Nanotopographical Gradient

The behavior of different cell types co-cultured on nanopillar arrays is described.  The authors find that co-cultured cells can be differentiated based on the different pillar sizes.  For example, they suggest that 75 nm tall pillars will maximize the ratio of endothelial cells to fibroblast cells in a co-culture.

Photochemistry and Liquid Crystals

From J. Am. Chem. Soc.:

Photoalignment Layers for Liquid Crystals from the Di-π-methane Rearrangement

The Swager group has used a clever di-pi-methane rearrangement along a polymer backbone to control liquid crystal alignment.

Ni-Catalyzed Cross Coupling

From J. Am. Chem. Soc.:

Nickel-Catalyzed Carbon–Carbon Bond-Forming Reactions of Unactivated Tertiary Alkyl Halides: Suzuki Arylations

The Fu group has reported a Ni-catalyzed cross-coupling of tertiary alkyl halides and 9-BBN functionalized aryl species.  They essentially used conditions they had developed previously for primary and secondary halides, but employed a smaller ligand.

A Supramolecular Cross-Linked Conjugated Polymer Network for Multiple Fluorescent Sensing

From J. Am. Chem. Soc.:

A Supramolecular Cross-Linked Conjugated Polymer Network for Multiple Fluorescent Sensing

A gel material was developed that displays turn on fluorescence in response to various stimuli.

Selective Fluorescent Detection of RNA in Living Cells by Using Imidazolium-Based Cyclophane

From J. Am. Chem. Soc.:

Selective Fluorescent Detection of RNA in Living Cells by Using Imidazolium-Based Cyclophane

An imidazolium-based cyclophane was found to display turn on fluorescence in the presence of RNA molecules.  Ionic interactions between the positively charged imidazolium groups and the anionic RNA backbond, along with pi-pi interactions, are invoked as reasons why this molecule selectively binds RNA.  In any case, the synthesis could be of interest to those of you working with NHCs.

H-Gemcitabine: A New Gemcitabine Prodrug for Treating Cancer

From Bioconj. Chem.:

H-Gemcitabine: A New Gemcitabine Prodrug for Treating Cancer

Synthesis and in vivo evaluation of a gemcitabine prodrug is described.  The synthesis deals with various thiol and thiol derivatives.  Could be useful for those of you making thiols.