Solvents can control solute molecular identity Nat. Chem. (IF 25.87) Pub Date : 2018-05-21 Devon. R. Widmer, Benjamin J. Schwartz
For solution-phase chemical reactions, the solvent is often considered simply as a medium to allow the reactants to encounter each other by diffusion. Although examples of direct solvent effects on molecular solutes exist, such as the compression of solute bonding electrons due to Pauli repulsion interactions, the solvent is not usually considered a part of the chemical species of interest. We show, using quantum simulations of Na2, that when there are local specific interactions between a solute and solvent that are energetically on the same order as a hydrogen bond, the solvent controls not only the bond dynamics but also the chemical identity of the solute. In tetrahydrofuran, dative bonding interactions between the solvent and Na atoms lead to unique coordination states that must cross a free energy barrier of ~8 kBT—undergoing a chemical reaction—to interconvert. Each coordination state has its own dynamics and spectroscopic signatures, highlighting the importance of considering the solvent in the identity of condensed-phase chemical systems.
Hitting the sweet spot Nat. Chem. (IF 25.87) Pub Date : 2018-05-21 Lara R. Malins
Hitting the sweet spotHitting the sweet spot, Published online: 21 May 2018; doi:10.1038/s41557-018-0071-2As the most abundant class of biomolecules on Earth, carbohydrates are implicated in a multitude of biological functions. Now, a simple chemical transformation has enabled the direct and selective installation of carbohydrates onto a diverse range of small molecules and peptides.
A new fundamental type of conformational isomerism Nat. Chem. (IF 25.87) Pub Date : 2018-05-21 Peter J. Canfield, Iain M. Blake, Zheng-Li Cai, Ian J. Luck, Elmars Krausz, Rika Kobayashi, Jeffrey R. Reimers, Maxwell J. Crossley
Isomerism is a fundamental chemical concept, reflecting the fact that the arrangement of atoms in a molecular entity has a profound influence on its chemical and physical properties. Here we describe a previously unclassified fundamental form of conformational isomerism through four resolved stereoisomers of a transoid (BF)O(BF)-quinoxalinoporphyrin. These comprise two pairs of enantiomers that manifest structural relationships not describable within existing IUPAC nomenclature and terminology. They undergo thermal diastereomeric interconversion over a barrier of 104 ± 2 kJ mol−1, which we term ‘akamptisomerization’. Feasible interconversion processes between conceivable synthesis products and reaction intermediates were mapped out by density functional theory calculations, identifying bond-angle inversion (BAI) at a singly bonded atom as the reaction mechanism. We also introduce the necessary BAI stereodescriptors parvo and amplo. Based on an extended polytope formalism of molecular structure and stereoisomerization, BAI-driven akamptisomerization is shown to be the final fundamental type of conformational isomerization.
Vibrations that live long and prosper Nat. Chem. (IF 25.87) Pub Date : 2018-05-21 Arthur L. Utz
Vibrations that live long and prosperVibrations that live long and prosper, Published online: 21 May 2018; doi:10.1038/s41557-018-0072-1Molecular vibrations can be highly effective promoters of gas-phase chemistry. Now, measurements show that excited vibrational states can survive on metal surfaces far longer than expected — reshaping our understanding of how vibrational excitation might also promote or modify heterogeneously catalysed chemistry on metals.
Identification and characterization of diverse coherences in the Fenna–Matthews–Olson complex Nat. Chem. (IF 25.87) Pub Date : 2018-05-21 Erling Thyrhaug, Roel Tempelaar, Marcelo J. P. Alcocer, Karel Žídek, David Bína, Jasper Knoester, Thomas L. C. Jansen, Donatas Zigmantas
The idea that excitonic (electronic) coherences are of fundamental importance to natural photosynthesis gained popularity when slowly dephasing quantum beats (QBs) were observed in the two-dimensional electronic spectra of the Fenna–Matthews–Olson (FMO) complex at 77 K. These were assigned to superpositions of excitonic states, a controversial interpretation, as the strong chromophore–environment interactions in the complex suggest fast dephasing. Although it has been pointed out that vibrational motion produces similar spectral signatures, a concrete assignment of these oscillatory signals to distinct physical processes is still lacking. Here we revisit the coherence dynamics of the FMO complex using polarization-controlled two-dimensional electronic spectroscopy, supported by theoretical modelling. We show that the long-lived QBs are exclusively vibrational in origin, whereas the dephasing of the electronic coherences is completed within 240 fs even at 77 K. We further find that specific vibrational coherences are produced via vibronically coupled excited states. The presence of such states suggests that vibronic coupling is relevant for photosynthetic energy transfer.
Communicating catalysts Nat. Chem. (IF 25.87) Pub Date : 2018-05-21 Bert M. Weckhuysen
Communicating catalystsCommunicating catalysts, Published online: 21 May 2018; doi:10.1038/s41557-018-0069-9The beauty and activity of enzymes inspire chemists to tailor new and better non-biological catalysts. Now, a study reveals that the active sites within heterogeneous catalysts actively cooperate in a fashion phenomenologically similar to, but mechanistically distinct, from enzymes.
Tritium trinkets Nat. Chem. (IF 25.87) Pub Date : 2018-05-21 Brett F. Thornton, Shawn C. Burdette
Tritium trinketsTritium trinkets, Published online: 21 May 2018; doi:10.1038/s41557-018-0070-3Scientists take nomenclature seriously, but tritium was named in a casual aside. Brett F. Thornton and Shawn C. Burdette discuss the heavy, radioactive hydrogen isotope that is available for purchase online.
Enrichment-triggered prodrug activation demonstrated through mitochondria-targeted delivery of doxorubicin and carbon monoxide Nat. Chem. (IF 25.87) Pub Date : 2018-05-14 Yueqin Zheng, Xingyue Ji, Bingchen Yu, Kaili Ji, David Gallo, Eva Csizmadia, Mengyuan Zhu, Manjusha Roy Choudhury, Ladie Kimberly C. De La Cruz, Vayou Chittavong, Zhixiang Pan, Zhengnan Yuan, Leo E. Otterbein, Binghe Wang
Controlled activation is a critical component in prodrug development. Here we report a concentration-sensitive platform approach for bioorthogonal prodrug activation by taking advantage of reaction kinetics. Using two ‘click and release’ systems, we demonstrate enrichment and prodrug activation specifically in mitochondria to demonstrate the principle of the approach. In both cases, the payload (doxorubicin or carbon monoxide) was released inside the mitochondrial matrix following the enrichment-initiated click reaction. Furthermore, mitochondria-targeted delivery yielded substantial augmentation of functional biological and therapeutic effects in vitro and in vivo when compared to controls, which did not result in enrichment. This method is thus a platform for targeted drug delivery that is amenable to conjugation with a variety of molecules and is not limited to cell-surface delivery. Taken together, these two 'click and release' pairs clearly demonstrate the concept of enrichment-triggered drug release and the critical feasibility of treating clinically relevant diseases such as acute liver injury and cancer.
Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus Nat. Chem. (IF 25.87) Pub Date : 2018-05-14 Aurélie Mousnier, Andrew S. Bell, Dawid P. Swieboda, Julia Morales-Sanfrutos, Inmaculada Pérez-Dorado, James A. Brannigan, Joseph Newman, Markus Ritzefeld, Jennie A. Hutton, Anabel Guedán, Amin S. Asfor, Sean W. Robinson, Iva Hopkins-Navratilova, Anthony J. Wilkinson, Sebastian L. Johnston, Robin J. Leatherbarrow, Tobias J. Tuthill, Roberto Solari, Edward W. Tate
Rhinoviruses (RVs) are the pathogens most often responsible for the common cold, and are a frequent cause of exacerbations in asthma, chronic obstructive pulmonary disease and cystic fibrosis. Here we report the discovery of IMP-1088, a picomolar dual inhibitor of the human N-myristoyltransferases NMT1 and NMT2, and use it to demonstrate that pharmacological inhibition of host-cell N-myristoylation rapidly and completely prevents rhinoviral replication without inducing cytotoxicity. The identification of cooperative binding between weak-binding fragments led to rapid inhibitor optimization through fragment reconstruction, structure-guided fragment linking and conformational control over linker geometry. We show that inhibition of the co-translational myristoylation of a specific virus-encoded protein (VP0) by IMP-1088 potently blocks a key step in viral capsid assembly, to deliver a low nanomolar antiviral activity against multiple RV strains, poliovirus and foot and-mouth disease virus, and protection of cells against virus-induced killing, highlighting the potential of host myristoylation as a drug target in picornaviral infections.
Harvesting multiple electron–hole pairs generated through plasmonic excitation of Au nanoparticles Nat. Chem. (IF 25.87) Pub Date : 2018-05-07 Youngsoo Kim, Jeremy G. Smith, Prashant K. Jain
Multi-electron redox reactions, although central to artificial photosynthesis, are kinetically sluggish. Amidst the search for synthetic catalysts for such processes, plasmonic nanoparticles have been found to catalyse multi-electron reduction of CO2 under visible light. This example motivates the need for a general, insight-driven framework for plasmonic catalysis of such multi-electron chemistry. Here, we elucidate the principles underlying the extraction of multiple redox equivalents from a plasmonic photocatalyst. We measure the kinetics of electron harvesting from a gold nanoparticle photocatalyst as a function of photon flux. Our measurements, supported by theoretical modelling, reveal a regime where two-electron transfer from the excited gold nanoparticle becomes prevalent. Multiple electron harvesting becomes possible under continuous-wave, visible-light excitation of moderate intensity due to strong interband transitions in gold and electron–hole separation accomplished using a hole scavenger. These insights will help expand the utility of plasmonic photocatalysis beyond CO2 reduction to other challenging multi-electron, multi-proton transformations such as N2 fixation.
Two-dimensional Na–Cl crystals of unconventional stoichiometries on graphene surface from dilute solution at ambient conditions Nat. Chem. (IF 25.87) Pub Date : 2018-05-07 Guosheng Shi, Liang Chen, Yizhou Yang, Deyuan Li, Zhe Qian, Shanshan Liang, Long Yan, Lu Hua Li, Minghong Wu, Haiping Fang
NaCl in a 1:1 stoichiometry is the only known stable form of the Na–Cl crystal under ambient conditions, and non-1:1 Na–Cl species can only form under extreme conditions, such as high pressures. Here we report the direct observation, under ambient conditions, of Na2Cl and Na3Cl as two-dimensional (2D) Na–Cl crystals, together with regular NaCl, on reduced graphene oxide membranes and on the surfaces of natural graphite powders from salt solutions far below the saturated concentration. Molecular dynamics and density functional theory calculations suggest that this unconventional crystallization process originates from the cation–π interaction between the ions and the π-conjugated system in the graphitic surface, which promotes the ion–surface adsorption. The strong Na+–π interaction and charge transfer lead to stoichiometries with an excess of Na+. With unique electron and spin distributions and bonding, the resulting 2D crystals may have unusual electronic, magnetic, optical and mechanical properties.
Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes Nat. Chem. (IF 25.87) Pub Date : 2018-05-07 Johnny Habchi, Sean Chia, Céline Galvagnion, Thomas C. T. Michaels, Mathias M. J. Bellaiche, Francesco Simone Ruggeri, Michele Sanguanini, Ilaria Idini, Janet R. Kumita, Emma Sparr, Sara Linse, Christopher M. Dobson, Tuomas P. J. Knowles, Michele Vendruscolo
Alzheimer’s disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer’s disease, the detailed mechanistic link between this lipid molecule and the disease process remains to be fully established. To address this problem, we adopt a kinetics-based strategy that reveals a specific catalytic role of cholesterol in the aggregation of Aβ42 (the 42-residue form of the amyloid-β peptide). More specifically, we demonstrate that lipid membranes containing cholesterol promote Aβ42 aggregation by enhancing its primary nucleation rate by up to 20-fold through a heterogeneous nucleation pathway. We further show that this process occurs as a result of cooperativity in the interaction of multiple cholesterol molecules with Aβ42. These results identify a specific microscopic pathway by which cholesterol dramatically enhances the onset of Aβ42 aggregation, thereby helping rationalize the link between Alzheimer’s disease and the impairment of cholesterol homeostasis.
Cyclization of peptides with two chemical bridges affords large scaffold diversities Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Sangram S. Kale, Camille Villequey, Xu-Dong Kong, Alessandro Zorzi, Kaycie Deyle, Christian Heinis
Successful screening campaigns depend on large and structurally diverse collections of compounds. In macrocycle screening, variation of the molecular scaffold is important for structural diversity, but so far it has been challenging to diversify this aspect in large combinatorial libraries. Here, we report the cyclization of peptides with two chemical bridges to provide rapid access to thousands of different macrocyclic scaffolds in libraries that are easy to synthesize, screen and decode. Application of this strategy to phage-encoded libraries allowed for the screening of an unprecedented structural diversity of macrocycles against plasma kallikrein, which is important in the swelling disorder hereditary angioedema. These libraries yielded inhibitors with remarkable binding properties (subnanomolar Ki, >1,000-fold selectivity) despite the small molecular mass (~1,200 Da). An interlaced bridge format characteristic of this strategy provided high proteolytic stability (t1/2 in plasma of >3 days), making double-bridged peptides potentially amenable to topical or oral delivery.
Manganese-catalysed benzylic C(sp3)–H amination for late-stage functionalization Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Joseph R. Clark, Kaibo Feng, Anasheh Sookezian, M. Christina White
Reactions that directly install nitrogen into C–H bonds of complex molecules are significant because of their potential to change the chemical and biological properties of a given compound. Although selective intramolecular C–H amination reactions are known, achieving high levels of reactivity while maintaining excellent site selectivity and functional-group tolerance remains a challenge for intermolecular C–H amination. Here, we report a manganese perchlorophthalocyanine catalyst [MnIII(ClPc)] for intermolecular benzylic C–H amination of bioactive molecules and natural products that proceeds with unprecedented levels of reactivity and site selectivity. In the presence of a Brønsted or Lewis acid, the [MnIII(ClPc)]-catalysed C–H amination demonstrates unique tolerance for tertiary amine, pyridine and benzimidazole functionalities. Mechanistic studies suggest that C–H amination likely proceeds through an electrophilic metallonitrene intermediate via a stepwise pathway where C–H cleavage is the rate-determining step of the reaction. Collectively, these mechanistic features contrast with previous base–metal-catalysed C–H aminations and provide new opportunities for tunable selectivities.
Ring-through-ring molecular shuttling in a saturated rotaxane Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Kelong Zhu, Giorgio Baggi, Stephen J. Loeb
Mechanically interlocked molecules such as rotaxanes and catenanes comprise two or more components whose motion relative to each other can be controlled. A rotaxane molecular shuttle, for example, consists of an axle bearing two recognition sites and a single macrocyclic wheel that can undergo a to-and-fro motion along the axle—shuttling between the recognition sites. The ability of mechanically interlocked molecules to undergo this type of large-amplitude change is the core mechanism behind almost every interlocked molecular switch or machine, including sophisticated mechanical systems such as a molecular elevator and a peptide synthesizer. Here, as a way to expand the scope of dynamics possible at the molecular level, we have developed a molecular shuttling mechanism involving the exchange of rings between two recognition sites in a saturated rotaxane (one with no empty recognition sites). This was accomplished by passing a smaller ring through a larger one, thus achieving ring-through-ring molecular shuttling.
Dynamic actuation of glassy polymersomes through isomerization of a single azobenzene unit at the block copolymer interface Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Mijanur Rahaman Molla, Poornima Rangadurai, Lucas Antony, Subramani Swaminathan, Juan J. de Pablo, S. Thayumanavan
Nature has engineered exquisitely responsive systems where molecular-scale information is transferred across an interface and propagated over long length scales. Such systems rely on multiple interacting, signalling and adaptable molecular and supramolecular networks that are built on dynamic, non-equilibrium structures. Comparable synthetic systems are still in their infancy. Here, we demonstrate that the light-induced actuation of a molecularly thin interfacial layer, assembled from a hydrophilic- azobenzene -hydrophobic diblock copolymer, can result in a reversible, long-lived perturbation of a robust glassy membrane across a range of over 500 chemical bonds. We show that the out-of-equilibrium actuation is caused by the photochemical trans–cis isomerization of the azo group, a single chemical functionality, in the middle of the interfacial layer. The principles proposed here are implemented in water-dispersed nanocapsules, and have implications for on-demand release of embedded cargo molecules.
Engineering the entropy-driven free-energy landscape of a dynamic nanoporous protein assembly Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Robert Alberstein, Yuta Suzuki, Francesco Paesani, F. Akif Tezcan
De novo design and construction of stimuli-responsive protein assemblies that predictably switch between discrete conformational states remains an essential but highly challenging goal in biomolecular design. We previously reported synthetic, two-dimensional protein lattices self-assembled via disulfide bonding interactions, which endows them with a unique capacity to undergo coherent conformational changes without losing crystalline order. Here, we carried out all-atom molecular dynamics simulations to map the free-energy landscape of these lattices, validated this landscape through extensive structural characterization by electron microscopy and established that it is predominantly governed by solvent reorganization entropy. Subsequent redesign of the protein surface with conditionally repulsive electrostatic interactions enabled us to predictably perturb the free-energy landscape and obtain a new protein lattice whose conformational dynamics can be chemically and mechanically toggled between three different states with varying porosities and molecular densities.
Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Tyler J. Wadzinski, Angela Steinauer, Liana Hie, Guillaume Pelletier, Alanna Schepartz, Scott J. Miller
Glycosylated natural products and synthetic glycopeptides represent a significant and growing source of biochemical probes and therapeutic agents. However, methods that enable the aqueous glycosylation of endogenous amino acid functionality in peptides without the use of protecting groups are scarce. Here, we report a transformation that facilitates the efficient aqueous O-glycosylation of phenolic functionality in a wide range of small molecules, unprotected tyrosine, and tyrosine residues embedded within a range of complex, fully unprotected peptides. The transformation, which uses glycosyl fluoride donors and is promoted by Ca(OH)2, proceeds rapidly at room temperature in water, with good yields and selective formation of unique anomeric products depending on the stereochemistry of the glycosyl donor. High functional group tolerance is observed, and the phenol glycosylation occurs selectively in the presence of virtually all side chains of the proteinogenic amino acids with the singular exception of Cys. This method offers a highly selective, efficient, and operationally simple approach for the protecting-group-free synthesis of O-aryl glycosides and Tyr-O-glycosylated peptides in water.
A molecular multi-gene classifier for disease diagnostics Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Randolph Lopez, Ruofan Wang, Georg Seelig
Despite its early promise as a diagnostic and prognostic tool, gene expression profiling remains cost-prohibitive and challenging to implement in a clinical setting. Here, we introduce a molecular computation strategy for analysing the information contained in complex gene expression signatures without the need for costly instrumentation. Our workflow begins by training a computational classifier on labelled gene expression data. This in silico classifier is then realized at the molecular level to enable expression analysis and classification of previously uncharacterized samples. Classification occurs through a series of molecular interactions between RNA inputs and engineered DNA probes designed to differentially weigh each input according to its importance. We validate our technology with two applications: a classifier for early cancer diagnostics and a classifier for differentiating viral and bacterial respiratory infections based on host gene expression. Together, our results demonstrate a general and modular framework for low-cost gene expression analysis.
Amino-acid-encoded biocatalytic self-assembly enables the formation of transient conducting nanostructures Nat. Chem. (IF 25.87) Pub Date : 2018-04-30 Mohit Kumar, Nicole L. Ing, Vishal Narang, Nadeesha K. Wijerathne, Allon I. Hochbaum, Rein V. Ulijn
Aqueous compatible supramolecular materials hold promise for applications in environmental remediation, energy harvesting and biomedicine. One remaining challenge is to actively select a target structure from a multitude of possible options, in response to chemical signals, while maintaining constant, physiological conditions. Here, we demonstrate the use of amino acids to actively decorate a self-assembling core molecule in situ, thereby controlling its amphiphilicity and consequent mode of assembly. The core molecule is the organic semiconductor naphthalene diimide, functionalized with D- and L- tyrosine methyl esters as competing reactive sites. In the presence of α-chymotrypsin and a selected encoding amino acid, kinetic competition between ester hydrolysis and amidation results in covalent or non-covalent amino acid incorporation, and variable supramolecular self-assembly pathways. Taking advantage of the semiconducting nature of the naphthalene diimide core, electronic wires could be formed and subsequently degraded, giving rise to temporally regulated electro-conductivity.
Reversible calcium alloying enables a practical room-temperature rechargeable calcium-ion battery with a high discharge voltage Nat. Chem. (IF 25.87) Pub Date : 2018-04-23 Meng Wang, Chunlei Jiang, Songquan Zhang, Xiaohe Song, Yongbing Tang, Hui-Ming Cheng
Calcium-ion batteries (CIBs) are attractive candidates for energy storage because Ca2+ has low polarization and a reduction potential (−2.87 V versus standard hydrogen electrode, SHE) close to that of Li+ (−3.04 V versus SHE), promising a wide voltage window for a full battery. However, their development is limited by difficulties such as the lack of proper cathode/anode materials for reversible Ca2+ intercalation/de-intercalation, low working voltages (<2 V), low cycling stability, and especially poor room-temperature performance. Here, we report a CIB that can work stably at room temperature in a new cell configuration using graphite as the cathode and tin foils as the anode as well as the current collector. This CIB operates on a highly reversible electrochemical reaction that combines hexafluorophosphate intercalation/de-intercalation at the cathode and a Ca-involved alloying/de-alloying reaction at the anode. An optimized CIB exhibits a working voltage of up to 4.45 V with capacity retention of 95% after 350 cycles.
I-motif DNA structures are formed in the nuclei of human cells Nat. Chem. (IF 25.87) Pub Date : 2018-04-23 Mahdi Zeraati, David B. Langley, Peter Schofield, Aaron L. Moye, Romain Rouet, William E. Hughes, Tracy M. Bryan, Marcel E. Dinger, Daniel Christ
Human genome function is underpinned by the primary storage of genetic information in canonical B-form DNA, with a second layer of DNA structure providing regulatory control. I-motif structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Here we report the generation and characterization of an antibody fragment (iMab) that recognizes i-motif structures with high selectivity and affinity, enabling the detection of i-motifs in the nuclei of human cells. We demonstrate that the in vivo formation of such structures is cell-cycle and pH dependent. Furthermore, we provide evidence that i-motif structures are formed in regulatory regions of the human genome, including promoters and telomeric regions. Our results support the notion that i-motif structures provide key regulatory roles in the genome.
Direct observation of forward-scattering oscillations in the H+HD→H2+D reaction Nat. Chem. (IF 25.87) Pub Date : 2018-04-23 Daofu Yuan, Shengrui Yu, Wentao Chen, Jiwei Sang, Chang Luo, Tao Wang, Xin Xu, Piergiorgio Casavecchia, Xingan Wang, Zhigang Sun, Dong H. Zhang, Xueming Yang
Accurate measurements of product state-resolved angular distributions are central to fundamental studies of chemical reaction dynamics. Yet, fine quantum-mechanical structures in product angular distributions of a reactive scattering process, such as the fast oscillations in the forward-scattering direction, have never been observed experimentally and the nature of these oscillations has not been fully explored. Here we report the crossed-molecular-beam experimental observation of these fast forward-scattering oscillations in the product angular distribution of the benchmark chemical reaction, H + HD → H2 + D. Clear oscillatory structures are observed for the H2(v′ = 0, j′ = 1, 3) product states at a collision energy of 1.35 eV, in excellent agreement with the quantum-mechanical dynamics calculations. Our analysis reveals that the oscillatory forward-scattering components are mainly contributed by the total angular momentum J around 28. The partial waves and impact parameters responsible for the forward scatterings are also determined from these observed oscillations, providing crucial dynamics information on the transient reaction process.
Claim to FAME Nat. Chem. (IF 25.87) Pub Date : 2018-04-19 Alvaro Mata
Claim to FAME Claim to FAME, Published online: 19 April 2018; doi:10.1038/s41557-018-0049-0 Proteins are attractive material building blocks, yet their intrinsic functionality has remained largely untapped. Now, a protein-based material that exhibits controllable self-assembling behaviour has been prepared in a one-pot synthesis by simultaneous use of recombinant expression and post-translational modification.
Tweaking mechanosensors Nat. Chem. (IF 25.87) Pub Date : 2018-04-19 Bruce C. Gibb
Tweaking mechanosensors Tweaking mechanosensors, Published online: 19 April 2018; doi:10.1038/s41557-018-0051-6 Bruce C. Gibb discusses the biochemistry behind the sensory experiences associated with eating chillies and the lesser-known tingle-inducing ‘sanshools’.
Understanding the quantum nature of low-energy C(3P j ) + He inelastic collisions Nat. Chem. (IF 25.87) Pub Date : 2018-04-16 Astrid Bergeat, Simon Chefdeville, Michel Costes, Sébastien B. Morales, Christian Naulin, Uzi Even, Jacek Kłos, François Lique
Inelastic collisions that occur between open-shell atoms and other atoms or molecules, and that promote a spin–orbit transition, involve multiple interaction potentials. They are non-adiabatic by nature and cannot be described within the Born–Oppenheimer approximation; in particular, their theoretical modelling becomes very challenging when the collision energies have values comparable to the spin–orbit splitting. Here we study inelastic collisions between carbon in its ground state C(3Pj=0) and helium atoms—at collision energies in the vicinity of spin–orbit excitation thresholds (~0.2 and 0.5 kJ mol−1)—that result in spin–orbit excitation to C(3Pj=1) and C(3Pj=2). State-to-state integral cross-sections are obtained from crossed-beam experiments with a beam source that provides an almost pure beam of C(3Pj=0) . We observe very good agreement between experimental and theoretical results (acquired using newly calculated potential energy curves), which validates our characterization of the quantum dynamical resonances that are observed. Rate coefficients at very low temperatures suitable for chemical modelling of the interstellar medium are also calculated.
Tracing the ‘ninth sulfur’ of the nitrogenase cofactor via a semi-synthetic approach Nat. Chem. (IF 25.87) Pub Date : 2018-04-16 Kazuki Tanifuji, Chi Chung Lee, Nathaniel S. Sickerman, Kazuyuki Tatsumi, Yasuhiro Ohki, Yilin Hu, Markus W. Ribbe
The M-cluster is the [(homocitrate)MoFe7S9C] active site of nitrogenase that is derived from an 8Fe core assembled viacoupling and rearrangement of two [Fe4S4] clusters concomitant with the insertion of an interstitial carbon and a ‘ninth sulfur’. Combining synthetic [Fe4S4] clusters with an assembly protein template, here we show that sulfite can give rise to the ninth sulfur that is incorporated in the catalytically important belt region of the cofactor after the radical S-adenosyl-l-methionine-dependent carbide insertion and the concurrent 8Fe-core rearrangement have already taken place. Based on the differential reactivity of the formed cluster species, we also propose a new [Fe8S8C] cluster intermediate, the L*-cluster, which is similar to the [Fe8S9C] L-cluster, but lacks the ninth sulfur from sulfite. This work provides a semi-synthetic tool for protein reconstitution that could be widely applicable for the functional analysis of other FeS systems.
Cold quantum-controlled rotationally inelastic scattering of HD with H2 and D2 reveals collisional partner reorientation Nat. Chem. (IF 25.87) Pub Date : 2018-04-16 William E. Perreault, Nandini Mukherjee, Richard N. Zare
Molecular interactions are best probed by scattering experiments. Interpretation of these studies has been limited by lack of control over the quantum states of the incoming collision partners. We report here the rotationally inelastic collisions of quantum-state prepared deuterium hydride (HD) with H2 and D2 using a method that provides an improved control over the input states. HD was coexpanded with its partner in a single supersonic beam, which reduced the collision temperature to 0–5 K, and thereby restricted the involved incoming partial waves to s and p. By preparing HD with its bond axis preferentially aligned parallel and perpendicular to the relative velocity of the colliding partners, we observed that the rotational relaxation of HD depends strongly on the initial bond-axis orientation. We developed a partial-wave analysis that conclusively demonstrates that the scattering mechanism involves the exchange of internal angular momentum between the colliding partners. The striking differences between H2/HD and D2/HD scattering suggest the presence of anisotropically sensitive resonances.
Publisher Correction: O2−O2 and O2−N2 collision-induced absorption mechanisms unravelled Nat. Chem. (IF 25.87) Pub Date : 2018-04-13 Tijs Karman, Mark A. J. Koenis, Agniva Banerjee, David H. Parker, Iouli E. Gordon, Ad van der Avoird, Wim J. van der Zande, Gerrit C. Groenenboom
Publisher Correction: O2−O2 and O2−N2 collision-induced absorption mechanisms unravelled Publisher Correction: O2−O2 and O2−N2 collision-induced absorption mechanisms unravelled, Published online: 13 April 2018; doi:10.1038/s41557-018-0063-2 Publisher Correction: O2−O2 and O2−N2 collision-induced absorption mechanisms unravelled
Retraction Note: Catalytic living ring-opening metathesis polymerization Nat. Chem. (IF 25.87) Pub Date : 2018-04-11 Amit A. Nagarkar, Andreas F. M. Kilbinger
Retraction Note: Catalytic living ring-opening metathesis polymerization Retraction Note: Catalytic living ring-opening metathesis polymerization, Published online: 11 April 2018; doi:10.1038/s41557-018-0044-5 Retraction Note: Catalytic living ring-opening metathesis polymerization
O2−O2 and O2−N2 collision-induced absorption mechanisms unravelled Nat. Chem. (IF 25.87) Pub Date : 2018-04-09 Tijs Karman, Mark A. J. Koenis, Agniva Banerjee, David H. Parker, Iouli E. Gordon, Ad van der Avoird, Wim J. van der Zande, Gerrit C. Groenenboom
Collision-induced absorption is the phenomenon in which interactions between colliding molecules lead to absorption of light, even for transitions that are forbidden for the isolated molecules. Collision-induced absorption contributes to the atmospheric heat balance and is important for the electronic excitations of O2 that are used for remote sensing. Here, we present a theoretical study of five vibronic transitions in O2−O2 and O2−N2, using analytical models and numerical quantum scattering calculations. We unambiguously identify the underlying absorption mechanism, which is shown to depend explicitly on the collision partner—contrary to textbook knowledge. This explains experimentally observed qualitative differences between O2−O2 and O2−N2 collisions in the overall intensity, line shape and vibrational dependence of the absorption spectrum. It is shown that these results can be used to discriminate between conflicting experimental data and even to identify unphysical results, thus impacting future experimental studies and atmospheric applications.
High phase-purity 1T′-MoS2- and 1T′-MoSe2-layered crystals Nat. Chem. (IF 25.87) Pub Date : 2018-04-02 Yifu Yu, Gwang-Hyeon Nam, Qiyuan He, Xue-Jun Wu, Kang Zhang, Zhenzhong Yang, Junze Chen, Qinglang Ma, Meiting Zhao, Zhengqing Liu, Fei-Rong Ran, Xingzhi Wang, Hai Li, Xiao Huang, Bing Li, Qihua Xiong, Qing Zhang, Zheng Liu, Lin Gu, Yonghua Du, Wei Huang, Hua Zhang
Phase control plays an important role in the precise synthesis of inorganic materials, as the phase structure has a profound influence on properties such as conductivity and chemical stability. Phase-controlled preparation has been challenging for the metallic-phase group-VI transition metal dichalcogenides (the transition metals are Mo and W, and the chalcogens are S, Se and Te), which show better performance in electrocatalysis than their semiconducting counterparts. Here, we report the large-scale preparation of micrometre-sized metallic-phase 1T′-MoX2 (X = S, Se)-layered bulk crystals in high purity. We reveal that 1T′-MoS2 crystals feature a distorted octahedral coordination structure and are convertible to 2H-MoS2 following thermal annealing or laser irradiation. Electrochemical measurements show that the basal plane of 1T′-MoS2 is much more active than that of 2H-MoS2 for the electrocatalytic hydrogen evolution reaction in an acidic medium.
An artificial interphase enables reversible magnesium chemistry in carbonate electrolytes Nat. Chem. (IF 25.87) Pub Date : 2018-04-02 Seoung-Bum Son, Tao Gao, Steve P. Harvey, K. Xerxes Steirer, Adam Stokes, Andrew Norman, Chunsheng Wang, Arthur Cresce, Kang Xu, Chunmei Ban
Magnesium-based batteries possess potential advantages over their lithium counterparts. However, reversible Mg chemistry requires a thermodynamically stable electrolyte at low potential, which is usually achieved with corrosive components and at the expense of stability against oxidation. In lithium-ion batteries the conflict between the cathodic and anodic stabilities of the electrolytes is resolved by forming an anode interphase that shields the electrolyte from being reduced. This strategy cannot be applied to Mg batteries because divalent Mg2+ cannot penetrate such interphases. Here, we engineer an artificial Mg2+-conductive interphase on the Mg anode surface, which successfully decouples the anodic and cathodic requirements for electrolytes and demonstrate highly reversible Mg chemistry in oxidation-resistant electrolytes. The artificial interphase enables the reversible cycling of a Mg/V2O5 full-cell in the water-containing, carbonate-based electrolyte. This approach provides a new avenue not only for Mg but also for other multivalent-cation batteries facing the same problems, taking a step towards their use in energy-storage applications.
Second-generation DNA-templated macrocycle libraries for the discovery of bioactive small molecules Nat. Chem. (IF 25.87) Pub Date : 2018-04-02 Dmitry L. Usanov, Alix I. Chan, Juan Pablo Maianti, David R. Liu
DNA-encoded libraries have emerged as a widely used resource for the discovery of bioactive small molecules, and offer substantial advantages compared with conventional small-molecule libraries. Here, we have developed and streamlined multiple fundamental aspects of DNA-encoded and DNA-templated library synthesis methodology, including computational identification and experimental validation of a 20 × 20 × 20 × 80 set of orthogonal codons, chemical and computational tools for enhancing the structural diversity and drug-likeness of library members, a highly efficient polymerase-mediated template library assembly strategy, and library isolation and purification methods. We have integrated these improved methods to produce a second-generation DNA-templated library of 256,000 small-molecule macrocycles with improved drug-like physical properties. In vitro selection of this library for insulin-degrading enzyme affinity resulted in novel insulin-degrading enzyme inhibitors, including one of unusual potency and novel macrocycle stereochemistry (IC50 = 40 nM). Collectively, these developments enable DNA-templated small-molecule libraries to serve as more powerful, accessible, streamlined and cost-effective tools for bioactive small-molecule discovery.
Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA Nat. Chem. (IF 25.87) Pub Date : 2018-04-02 Krzysztof Ziach, Céline Chollet, Vincent Parissi, Panchami Prabhakaran, Mathieu Marchivie, Valentina Corvaglia, Partha Pratim Bose, Katta Laxmi-Reddy, Frédéric Godde, Jean-Marie Schmitter, Stéphane Chaignepain, Philippe Pourquier, Ivan Huc
Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein–DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known. Here, we report the design, synthesis and structural characterization of aromatic oligoamides that fold into single helical conformations and display a double helical array of negatively charged residues in positions that match the phosphate moieties in B-DNA. These molecules were able to inhibit several enzymes possessing non-sequence-selective DNA-binding properties, including topoisomerase 1 and HIV-1 integrase, presumably through specific foldamer–protein interactions, whereas sequence-selective enzymes were not inhibited. Such modular and synthetically accessible DNA mimics provide a versatile platform to design novel inhibitors of protein–DNA interactions.
Single-cell mRNA cytometry via sequence-specific nanoparticle clustering and trapping Nat. Chem. (IF 25.87) Pub Date : 2018-04-02 Mahmoud Labib, Reza M. Mohamadi, Mahla Poudineh, Sharif U. Ahmed, Ivaylo Ivanov, Ching-Lung Huang, Maral Moosavi, Edward H. Sargent, Shana O. Kelley
Cell-to-cell variation in gene expression creates a need for techniques that can characterize expression at the level of individual cells. This is particularly true for rare circulating tumour cells, in which subtyping and drug resistance are of intense interest. Here we describe a method for cell analysis—single-cell mRNA cytometry—that enables the isolation of rare cells from whole blood as a function of target mRNA sequences. This approach uses two classes of magnetic particles that are labelled to selectively hybridize with different regions of the target mRNA. Hybridization leads to the formation of large magnetic clusters that remain localized within the cells of interest, thereby enabling the cells to be magnetically separated. Targeting specific intracellular mRNAs enablescirculating tumour cells to be distinguished from normal haematopoietic cells. No polymerase chain reaction amplification is required to determine RNA expression levels and genotype at the single-cell level, and minimal cell manipulation is required. To demonstrate this approach we use single-cell mRNA cytometry to detect clinically important sequences in prostate cancer specimens.
Cooperative communication within and between single nanocatalysts Nat. Chem. (IF 25.87) Pub Date : 2018-03-26 Ningmu Zou, Xiaochun Zhou, Guanqun Chen, Nesha May Andoy, Won Jung, Guokun Liu, Peng Chen
Enzymes often show catalytic allostery in which reactions occurring at different sites communicate cooperatively over distances of up to a few nanometres. Whether such effects can occur with non-biological nanocatalysts remains unclear, even though these nanocatalysts can undergo restructuring and molecules can diffuse over catalyst surfaces. Here we report that phenomenologically similar, but mechanistically distinct, cooperative effects indeed exist for nanocatalysts. Using spatiotemporally resolved single-molecule catalysis imaging, we find that catalytic reactions on a single Pd or Au nanocatalyst can communicate with each other, probably via hopping of positively charged holes on the catalyst surface, over ~102 nanometres and with a temporal memory of ~101 to 102 seconds, giving rise to positive cooperativity among its surface active sites. Similar communication is also observed between individual nanocatalysts, however it operates via a molecular diffusion mechanism involving negatively charged product molecules, and its communication distance is many micrometres. Generalization of these long-range intra- and interparticle catalytic communication mechanisms may introduce a novel conceptual framework for understanding nanoscale catalysis.
Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide Nat. Chem. (IF 25.87) Pub Date : 2018-03-26 Samuel I. A. Cohen, Risto Cukalevski, Thomas C. T. Michaels, Anđela Šarić, Mattias Törnquist, Michele Vendruscolo, Christopher M. Dobson, Alexander K. Buell, Tuomas P. J. Knowles, Sara Linse
Mapping free-energy landscapes has proved to be a powerful tool for studying reaction mechanisms. Many complex biomolecular assembly processes, however, have remained challenging to access using this approach, including the aggregation of peptides and proteins into amyloid fibrils implicated in a range of disorders. Here, we generalize the strategy used to probe free-energy landscapes in protein folding to determine the activation energies and entropies that characterize each of the molecular steps in the aggregation of the amyloid-β peptide (Aβ42), which is associated with Alzheimer’s disease. Our results reveal that interactions between monomeric Aβ42 and amyloid fibrils during fibril-dependent secondary nucleation fundamentally reverse the thermodynamic signature of this process relative to primary nucleation, even though both processes generate aggregates from soluble peptides. By mapping the energetic and entropic contributions along the reaction trajectories, we show that the catalytic efficiency of Aβ42 fibril surfaces results from the enthalpic stabilization of adsorbing peptides in conformations amenable to nucleation, resulting in a dramatic lowering of the activation energy for nucleation.
Strategies for microbial synthesis of high-value phytochemicals Nat. Chem. (IF 25.87) Pub Date : 2018-03-22 Sijin Li, Yanran Li, Christina D. Smolke
Phytochemicals are of great pharmaceutical and agricultural importance, but often exhibit low abundance in nature. Recent demonstrations of industrial-scale production of phytochemicals in yeast have shown that microbial production of these high-value chemicals is a promising alternative to sourcing these molecules from native plant hosts. However, a number of challenges remain in the broader application of this approach, including the limited knowledge of plant secondary metabolism and the inefficient reconstitution of plant metabolic pathways in microbial hosts. In this Review, we discuss recent strategies to achieve microbial biosynthesis of complex phytochemicals, including strategies to: (1) reconstruct plant biosynthetic pathways that have not been fully elucidated by mining enzymes from native and non-native hosts or by enzyme engineering; (2) enhance plant enzyme activity, specifically cytochrome P450 activity, by improving efficiency, selectivity, expression or electron transfer; and (3) enhance overall reaction efficiency of multi-enzyme pathways by dynamic control, compartmentalization or optimization with the host’s metabolism. We also highlight remaining challenges to — and future opportunities of — this approach.
Foldamers wave to the ribosome Nat. Chem. (IF 25.87) Pub Date : 2018-03-22 Alanna Schepartz
Foldamers wave to the ribosome Foldamers wave to the ribosome, Published online: 22 March 2018; doi:10.1038/s41557-018-0036-5 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.
Made in translation Nat. Chem. (IF 25.87) Pub Date : 2018-03-22 John C. Chaput
Made in translation Made in translation, Published online: 22 March 2018; doi:10.1038/s41557-018-0034-7 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.
Organic synthesis provides opportunities to transform drug discovery Nat. Chem. (IF 25.87) Pub Date : 2018-03-22 David C. Blakemore, Luis Castro, Ian Churcher, David C. Rees, Andrew W. Thomas, David M. Wilson, Anthony Wood
Despite decades of ground-breaking research in academia, organic synthesis is still a rate-limiting factor in drug-discovery projects. Here we present some current challenges in synthetic organic chemistry from the perspective of the pharmaceutical industry and highlight problematic steps that, if overcome, would find extensive application in the discovery of transformational medicines. Significant synthesis challenges arise from the fact that drug molecules typically contain amines and N-heterocycles, as well as unprotected polar groups. There is also a need for new reactions that enable non-traditional disconnections, more C–H bond activation and late-stage functionalization, as well as stereoselectively substituted aliphatic heterocyclic ring synthesis, C–X or C–C bond formation. We also emphasize that syntheses compatible with biomacromolecules will find increasing use, while new technologies such as machine-assisted approaches and artificial intelligence for synthesis planning have the potential to dramatically accelerate the drug-discovery process. We believe that increasing collaboration between academic and industrial chemists is crucial to address the challenges outlined here.
Hidden hassium Nat. Chem. (IF 25.87) Pub Date : 2018-03-22 Michael A. Tarselli
Hidden hassium Hidden hassium, Published online: 22 March 2018; doi:10.1038/s41557-018-0037-4 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.
Experimental and computational evidence of halogen bonds involving astatine Nat. Chem. (IF 25.87) Pub Date : 2018-03-19 Ning Guo, Rémi Maurice, David Teze, Jérôme Graton, Julie Champion, Gilles Montavon, Nicolas Galland
The importance of halogen bonds—highly directional interactions between an electron-deficient σ-hole moiety in a halogenated compound and an acceptor such as a Lewis base—is being increasingly recognized in a wide variety of fields from biomedicinal chemistry to materials science. The heaviest halogens are known to form stronger halogen bonds, implying that if this trend continues down the periodic table, astatine should exhibit the highest halogen-bond donating ability. This may be mitigated, however, by the relativistic effects undergone by heavy elements, as illustrated by the metallic character of astatine. Here, the occurrence of halogen-bonding interactions involving astatine is experimentally evidenced. The complexation constants of astatine monoiodide with a series of organic ligands in cyclohexane solution were derived from distribution coefficient measurements and supported by relativistic quantum mechanical calculations. Taken together, the results show that astatine indeed behaves as a halogen-bond donor—a stronger one than iodine—owing to its much more electrophilic σ-hole.
Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold Nat. Chem. (IF 25.87) Pub Date : 2018-03-19 Yizhou Li, Roberto De Luca, Samuele Cazzamalli, Francesca Pretto, Davor Bajic, Jörg Scheuermann, Dario Neri
In nature, specific antibodies can be generated as a result of an adaptive selection and expansion of lymphocytes with suitable protein binding properties. We attempted to mimic antibody–antigen recognition by displaying multiple chemical diversity elements on a defined macrocyclic scaffold. Encoding of the displayed combinations was achieved using distinctive DNA tags, resulting in a library size of 35,393,112. Specific binders could be isolated against a variety of proteins, including carbonic anhydrase IX, horseradish peroxidase, tankyrase 1, human serum albumin, alpha-1 acid glycoprotein, calmodulin, prostate-specific antigen and tumour necrosis factor. Similar to antibodies, the encoded display of multiple chemical elements on a constant scaffold enabled practical applications, such as fluorescence microscopy procedures or the selective in vivo delivery of payloads to tumours. Furthermore, the versatile structure of the scaffold facilitated the generation of protein-specific chemical probes, as illustrated by photo-crosslinking.
Ribosomal synthesis and folding of peptide-helical aromatic foldamer hybrids Nat. Chem. (IF 25.87) Pub Date : 2018-03-19 Joseph M. Rogers, Sunbum Kwon, Simon J. Dawson, Pradeep K. Mandal, Hiroaki Suga, Ivan Huc
Translation, the mRNA-templated synthesis of peptides by the ribosome, can be manipulated to incorporate variants of the 20 cognate amino acids. Such approaches for expanding the range of chemical entities that can be produced by the ribosome may accelerate the discovery of molecules that can perform functions for which poorly folded, short peptidic sequences are ill suited. Here, we show that the ribosome tolerates some artificial helical aromatic oligomers, so-called foldamers. Using a flexible tRNA-acylation ribozyme—flexizyme—foldamers were attached to tRNA, and the resulting acylated tRNAs were delivered to the ribosome to initiate the synthesis of non-cyclic and cyclic foldamer–peptide hybrid molecules. Passing through the ribosome exit tunnel requires the foldamers to unfold. Yet foldamers encode sufficient folding information to influence the peptide structure once translation is completed. We also show that in cyclic hybrids, the foldamer portion can fold into a helix and force the peptide segment to adopt a constrained and stretched conformation.
Evidence for a vibrational phase-dependent isotope effect on the photochemistry of vision Nat. Chem. (IF 25.87) Pub Date : 2018-03-19 C. Schnedermann, X. Yang, M. Liebel, K. M. Spillane, J. Lugtenburg, I. Fernández, A. Valentini, I. Schapiro, M. Olivucci, P. Kukura, R. A. Mathies
Vibronic coupling is key to efficient energy flow in molecular systems and a critical component of most mechanisms invoking quantum effects in biological processes. Despite increasing evidence for coherent coupling of electronic states being mediated by vibrational motion, it is not clear how and to what degree properties associated with vibrational coherence such as phase and coupling of atomic motion can impact the efficiency of light-induced processes under natural, incoherent illumination. Here, we show that deuteration of the H11–C11=C12–H12 double-bond of the 11-cis retinal chromophore in the visual pigment rhodopsin significantly and unexpectedly alters the photoisomerization yield while inducing smaller changes in the ultrafast isomerization dynamics assignable to known isotope effects. Combination of these results with non-adiabatic molecular dynamics simulations reveals a vibrational phase-dependent isotope effect that we suggest is an intrinsic attribute of vibronically coherent photochemical processes.
Genetically encoded lipid–polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly Nat. Chem. (IF 25.87) Pub Date : 2018-03-19 Davoud Mozhdehi, Kelli M. Luginbuhl, Joseph R. Simon, Michael Dzuricky, Rüdiger Berger, H. Samet Varol, Fred C. Huang, Kristen L. Buehne, Nicholas R. Mayne, Isaac Weitzhandler, Mischa Bonn, Sapun H. Parekh, Ashutosh Chilkoti
Post-translational modification of proteins is a strategy widely used in biological systems. It expands the diversity of the proteome and allows for tailoring of both the function and localization of proteins within cells as well as the material properties of structural proteins and matrices. Despite their ubiquity in biology, with a few exceptions, the potential of post-translational modifications in biomaterials synthesis has remained largely untapped. As a proof of concept to demonstrate the feasibility of creating a genetically encoded biohybrid material through post-translational modification, we report here the generation of a family of three stimulus-responsive hybrid materials—fatty-acid-modified elastin-like polypeptides—using a one-pot recombinant expression and post-translational lipidation methodology. These hybrid biomaterials contain an amphiphilic domain, composed of a β-sheet-forming peptide that is post-translationally functionalized with a C14 alkyl chain, fused to a thermally responsive elastin-like polypeptide. They exhibit temperature-triggered hierarchical self-assembly across multiple length scales with varied structure and material properties that can be controlled at the sequence level.
Dynamic protein assembly by programmable DNA strand displacement Nat. Chem. (IF 25.87) Pub Date : 2018-03-12 Rebecca P. Chen, Daniel Blackstock, Qing Sun, Wilfred Chen
Abstract Inspired by the remarkable ability of natural protein switches to sense and respond to a wide range of environmental queues, here we report a strategy to engineer synthetic protein switches by using DNA strand displacement to dynamically organize proteins with highly diverse and complex logic gate architectures. We show that DNA strand displacement can be used to dynamically control the spatial proximity and the corresponding fluorescence resonance energy transfer between two fluorescent proteins. Performing Boolean logic operations enabled the explicit control of protein proximity using multi-input, reversible and amplification architectures. We further demonstrate the power of this technology beyond sensing by achieving dynamic control of an enzyme cascade. Finally, we establish the utility of the approach as a synthetic computing platform that drives the dynamic reconstitution of a split enzyme for targeted prodrug activation based on the sensing of cancer-specific miRNAs.
Sticky when wet Nat. Chem. (IF 25.87) Pub Date : 2018-03-12 Ji Chen, Angelos Michaelides
Sticky when wet Sticky when wet, Published online: 12 March 2018; doi:10.1038/s41557-018-0024-9 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.
Crystal phase-based epitaxial growth of hybrid noble metal nanostructures on 4H/fcc Au nanowires Nat. Chem. (IF 25.87) Pub Date : 2018-03-12 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
Crystal-phase engineering offers opportunities for the rational design and synthesis of noble metal nanomaterials with unusual crystal phases that normally do not exist in bulk materials. However, it remains a challenge to use these materials as seeds to construct heterometallic nanostructures with desired crystal phases and morphologies for promising applications such as catalysis. Here, we report a strategy for the synthesis of binary and ternary hybrid noble metal nanostructures. Our synthesized crystal-phase heterostructured 4H/fcc Au nanowires enable the epitaxial growth of Ru nanorods on the 4H phase and fcc-twin boundary in Au nanowires, resulting in hybrid Au–Ru nanowires. Moreover, the method can be extended to the epitaxial growth of Rh, Ru–Rh and Ru–Pt nanorods on the 4H/fcc Au nanowires to form unique hybrid nanowires. Importantly, the Au–Ru hybrid nanowires with tunable compositions exhibit excellent electrocatalytic performance towards the hydrogen evolution reaction in alkaline media.
Hydroxide diffuses slower than hydronium in water because its solvated structure inhibits correlated proton transfer Nat. Chem. (IF 25.87) Pub Date : 2018-03-12 Mohan Chen, Lixin Zheng, Biswajit Santra, Hsin-Yu Ko, Robert A. DiStasio Jr, Michael L. Klein, Roberto Car, Xifan Wu
Proton transfer via hydronium and hydroxide ions in water is ubiquitous. It underlies acid–base chemistry, certain enzyme reactions, and even infection by the flu. Despite two centuries of investigation, the mechanism underlying why hydroxide diffuses slower than hydronium in water is still not well understood. Herein, we employ state-of-the-art density-functional-theory-based molecular dynamics—with corrections for non-local van der Waals interactions, and self-interaction in the electronic ground state—to model water and hydrated water ions. At this level of theory, we show that structural diffusion of hydronium preserves the previously recognized concerted behaviour. However, by contrast, proton transfer via hydroxide is less temporally correlated, due to a stabilized hypercoordination solvation structure that discourages proton transfer. Specifically, the latter exhibits non-planar geometry, which agrees with neutron-scattering results. Asymmetry in the temporal correlation of proton transfer leads to hydroxide diffusing slower than hydronium.
Evolution of sequence-defined highly functionalized nucleic acid polymers Nat. Chem. (IF 25.87) Pub Date : 2018-03-05 Zhen Chen, Phillip A. Lichtor, Adrian P. Berliner, Jonathan C. Chen, David R. Liu
The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure–activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.
Control over phase separation and nucleation using a laser-tweezing potential Nat. Chem. (IF 25.87) Pub Date : 2018-03-05 Finlay Walton, Klaas Wynne
Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is still a poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid–liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter.
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