bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stapled Peptides as Potential Therapeutics
Authors: McDougall Laura , Jamieson Andrew G 
Published: March 2019

Abstract

Stapled peptides are an important class of conformationally constrained, bioactive α‐helical peptides. They have been used extensively as chemical probes for the regulation of protein–protein interactions (PPIs), with one currently progressing through late‐stage clinical trials as a peptide drug candidate. Their ability to interact with shallow protein–protein interfaces, which have previously proven to be challenging to target with small molecules, has led to their rapid uptake by the chemical biology and drug discovery communities. Stapled peptides overcome some of the undesirable physicochemical properties that limit the use of peptides as therapeutics. They generally exhibit good binding affinity and specificity as they aim to accurately reproduce the α‐helix recognition motif from a PPI interface. They are protease resistant and in some instances have shown good cell permeability. The development of stapled peptides has thus resulted in a transformative shift by validating difficult PPIs as therapeutic targets and providing promising drug candidates.

Key Concepts

Stapled peptides are conformationally constrained α‐helical peptides.

Stapling reduces the entropic penalty of folding to produce the bioactive conformation, thus giving an increase in binding affinity over an unfolded peptide.

Through mimicking the interface these compounds have good binding affinity and specificity.

Proteolytic stability is enhanced through the induction of secondary structure and the effective shielding of the peptide backbone from recognition by protease enzymes.

Cell permeability can be enhanced by peptide stapling as the distribution of lipophilicity compared to the native peptide is altered.

Key PPIs implicated in cancer, including p53‐MDM2/MDMX, Aurora‐A/TPX2 and the Bcl family, have been probed using stapled peptides.
Structural Engineering of Cathode Materials for Lithium–Sulfur Batteries
Authors: Li Ligui , Yu Jingping , Wang Nan , Zhao Jun , Fan Bin , Zeng Shuaibo , Chen Shaowei 
Published: March 2019

Abstract
Lithium–sulfur (Li–S) battery represents a high‐performance energy storage technology that will find applications in diverse areas, such as stationary and portable electronics as well as electric vehicles. Yet, dissolution of lithium polysulfides from cathode into organic electrolytes and the subsequent diffusion toward anode are two primary challenges that compromise the battery performance and hamper its wide‐spread commercialization. Deliberate manipulation of the sulfur cathode by physical confinement, covalent formation of polymeric sulfur, and incorporation of chemically binding materials has been extensively reported in the literature for improving the corresponding cycling stability and other key electrochemical properties. In this article, we summarize recent key progress in structural engineering of cathode materials in the enhancement of the device performance and conclude with a perspective of the promises and challenges of Li–S battery technology.
Effect of Tui Na on upper limb spasticity after stroke: a randomized clinical trial
Authors: Wang Meng , Liu Shouguo , Peng Zhihang , Zhu Yi , Feng Xiaodong , Gu Yihuang , Sun Jianhua , Tang Qiang , Chen Hongxia , Huang Xiaolin , Hu Jun , Chen Wei , Xiang Jie , Wan Chunxiao , Fan Gangqi , Lu Jianhu , Xia Wenguang , Chen Liping , Wang Lihua , Lu Xiao , Li Jianan 
Published: March 2019

AbstractObjectiveTo investigate the efficacy and safety of Tui Na for treating spasticity of the upper limbs of stroke patients.DesignA prospective, multicenter, blinded, randomized controlled intervention study.SubjectsStroke patients with upper limb spasticity who were treated between December 2013 and February 2017 in 16 participating institutions in China were randomly assigned to receive either Tui Na plus conventional rehabilitation (Tui Na group, n = 222,) or conventional rehabilitation only (control group, n = 222).MethodsEligible adult patients (aged 18–75 years) were enrolled 1–12 months after stroke and randomly allocated in a 1:1 ratio to the two groups. Outcome assessors were blinded to treatment allocation. Muscle tone in the spastic muscles was evaluated using the Modified Ashworth Scale (MAS), and the primary endpoint was the change in MAS score over 4 weeks of treatment.ResultsAmong patients who had experienced stroke 1–3 months before treatment, the Tui Na group experienced significantly greater reductions in MAS scores for three muscle groups than did the control group after 4 weeks of treatment. These improvements were sustained at the 3‐ and 6‐month follow‐ups. However, among patients who suffered from stroke 4–6 months and 7–12 months before treatment, the change in MAS with treatment did not differ significantly between those who did and those who did not receive Tui Na. No Tui Na‐related adverse events during treatment were reported the groups.ConclusionTui Na was effective and safe for alleviating poststroke spasticity within 1–3 months after stroke onset.
Permanent Hydrophilization and Generic Bioactivation of Melt Electrowritten Scaffolds
Authors: Bertlein Sarah , Hochleitner Gernot , Schmitz Michael , Tessmar Jörg , Raghunath Michael , Dalton Paul D. , Groll Jürgen 
Published: March 2019

AbstractMelt electrowriting (MEW) is an emerging additive manufacturing technology that direct‐writes low‐micron diameter fibers into 3D scaffolds with high porosities. Often, the polymers currently used for MEW are hydrophobic thermoplastics that induce unspecific protein adsorption and subsequent uncontrolled cell adhesion. Here are developed a coating strategy for MEW scaffolds based on six‐arm star‐shaped NCO‐poly(ethylene oxide‐stat‐propylene oxide) (sP(EO‐stat‐PO)). This permanently hydrophilizes the PCL through the formation of a hydrogel coating and minimizes unspecific interactions with proteins and cells. It also provides the option of simultaneous covalent attachment of bioactive molecules through reaction with isocyanates before these are hydrolyzed. Furthermore, a photoactivatable chemical functionalization is introduced that is not dependent on the time‐limited window of isocyanate chemistry. For this, photo‐leucine is covalently immobilized into the sP(EO‐stat‐PO) layer, resulting in a photoactivatable scaffold that enables the binding of sterically demanding molecules at any timepoint after scaffold preparation and coating and is decoupled from the isocyanate chemistry. A successful biofunctionalization of MEW scaffolds via this strategy is demonstrated with streptavidin and collagen as examples. This hydrogel coating system is a generic one that introduces flexible specific and multiple surface functionalization, potentially for a spectrum of polymers made from different manufacturing processes.
Controlling the Output of Organic Micro/Nanolasers
Authors: Dong Haiyun , Zhang Chunhuan , Zhao Yong Sheng 
Published: March 2019

AbstractOrganic micro/nanolasers hold a promising potential in advancing the fields of photonics and optoelectronics. Recently, great progress has been made in designing and controlling the output characteristics of organic micro/nanolasers, which significantly expands the capabilities and improves the performance of micro/nanolasers. In this Progress Report, the design philosophy, research progress, and further research directions in manipulating the output behaviors of organic micro/nanolasers are presented. A brief introduction to the fundamentals of the organic micro/nanolasers is given with an emphasis on the basic principle for laser output control. Various organic micro/nanolasers with desired output are discussed in detail, including wavelength tunable lasers, multiwavelength lasers, mode controllable lasers, and directional lasers. Special emphasis is put on gaining insight into the structure–property relationship in the controllable organic micro/nanolasers. Finally, future research directions and challenges toward more advanced control strategies of organic micro/nanolasers are provided to give an outlook on this emerging field.
An Organocatalytic Two‐atom Ring Expansion Approach to Optically Active Glutarimides
Authors: Wei Yun‐Long , Ren Yajun , Mailhol Damien , Rajzmann Michel , Rodriguez Jean , Coquerel Yoann 
Published: March 2019

AbstractAn original two‐step organocatalytic synthesis of optically active glutarimides from 2‐oxocyclobutane carboxamides is described featuring an isothiourea‐catalyzed two‐atom ring‐expansive rearrangement.magnified image
Absolute Quantifizierung nicht‐kodierender RNA‐Spezies mittels Mikroskala‐Thermophorese
Authors: Jacob Dominik , Thüring Kathrin , Galliot Aurellia , Marchand Virginie , Galvanin Adeline , Ciftci Akif , Scharmann Karin , Stock Michael , Roignant Jean‐Yves , Leidel Sebastian A. , Motorin Yuri , Schaffrath Raffael , Klassen Roland , Helm Mark 
Published: March 2019

AbstractDie genaue Quantifizierung nicht‐kodierender RNA‐Spezies hat sich in jüngerer Zeit als dringendes Problem herauskristallisiert, das unter anderem Anwendung in der RNA‐Modifikationsanalytik, der Untersuchung von Gewebedifferenzierung und vielen anderen Bereichen findet. Wir stellen hier einen hybridisierungsbasierten Ansatz vor, der die Mikroskala‐Thermophorese (MST) als sehr schnelles und hochpräzises Verfahren verwendet, um z. B. einzelne tRNA‐Spezies mit einer Durchlaufzeit von etwa einer Stunde zu quantifizieren. Mithilfe der MST wurde u. a. die Wirkung von tRNA‐Toxinen, Hitzestress sowie von RNA‐Modifikationen auf einzelne tRNA‐Spezies untersucht. Eine vergleichende Analyse ergab weiterhin signifikante Unterschiede zu RNA‐Seq‐basierten Quantifizierungsansätzen, was auf eine Verzerrung letzterer aufgrund von tRNA‐Modifikationen hindeutet. Weitere Anwendung fand die Methode bei der Bestimmung von rRNA sowie von PolyA‐Fraktionen in zellulärer RNA.
High‐Throughput Reaction Screening with Nanomoles of Solid Reagents Coated on Glass Beads
Authors: Tu Noah P. , Dombrowski Amanda W. , Goshu Gashaw M. , Vasudevan Anil , Djuric Stevan W. , Wang Ying 
Published: March 2019

AbstractTechnologies that enable rapid screening of diverse reaction conditions are of critical importance to methodology development and reaction optimization, especially when molecules of high complexity and scarcity are involved. The lack of a general solid dispensing method for chemical reagents on micro‐ and nanomole scale prevents the full utilization of reaction screening technologies. We herein report the development of a technology in which glass beads coated with solid chemical reagents (ChemBeads) enable the delivery of nanomole quantities of solid chemical reagents efficiently. By exploring the concept of preferred screening sets, the flexibility and generality of this technology for high‐throughput reaction screening was validated.
Neue Entwicklungen auf dem Gebiet der Minisci‐Reaktion
Authors: Proctor Rupert S. J. , Phipps Robert J. 
Published: March 2019

AbstractReaktionen, die über die Addition von kohlenstoffzentrierten Radikalen an basische Heteroarene gefolgt von der formalen Abspaltung eines Wasserstoffatoms verlaufen, sind heute allgemein als Minisci‐Reaktionen bekannt. Als synthetisches Werkzeug erstmals in den 1960er Jahren von Minisci entwickelt, wurde diese Reaktion in den letzten fünfzig Jahren kontinuierlich genutzt, um Heterozyklen schnell und direkt zu funktionalisieren, ohne dass eine De‐novo‐Synthese von Heterozyklen nötig ist. Während die meisten der ursprünglich beschriebenen Syntheseprotokolle zur Radikalerzeugung auch heute noch genutzt werden, wurde in den vergangenen Jahren eine Reihe neuer Strategien zur Erzeugung von Radikalen entwickelt, die den Einsatz vielfältigerer Radikalvorläufer und milderer Reaktionsbedingungen ermöglichen. Das in den letzten Jahren gestiegene Interesse an neuen Umsetzungen mit freien Radikalen hat dazu geführt, dass Synthesechemikern heute eine Vielzahl von Möglichkeiten für eine Minisci‐Reaktion zur Verfügung stehen. Inzwischen sind zusätzlich zu Methoden, die die thermische Spaltung oder In‐situ‐Bildung reaktiver Radikalvorläufer nutzen, auch die Photoredoxkatalyse und die Elektrochemie als Strategien zur Radikalerzeugung etabliert. Dieser Aufsatz deckt die bemerkenswert umfangreiche Literatur ab, die in den letzten Jahren auf diesem Gebiet erschienen ist, und unternimmt so den Versuch, Chemikern eine Orientierungshilfe zu geben und gleichzeitig eine Perspektive über die Herausforderungen zu bieten, die bereits bewältigt wurden und offen bleiben. Neben den logischen Klassifizierungen dieser Fortschritte entsprechend der Art des jeweiligen Radikalvorläufers, auf die sich die meisten Arbeiten konzentrieren, werden in diesem Aufsatz auch aktuelle Fortschritte in der Kontrolle verschiedener Selektivitätsaspekte von Minisci‐Reaktionen diskutiert.
Towards Novel Photodynamic Anticancer Agents Generating Superoxide Anion Radicals: A Cyclometalated IrIIIComplex Conjugated to a Far‐Red Emitting Coumarin
Authors: Novohradsky Vojtech , Rovira Anna , Hally Cormac , Galindo Alex , Vigueras Gloria , Gandioso Albert , Svitelova Marie , Bresolí‐Obach Roger , Kostrhunova Hana , Markova Lenka , Kasparkova Jana , Nonell Santi , Ruiz José , Brabec Viktor , Marchán Vicente 
Published: March 2019

AbstractAlthough cyclometalated IrIIIcomplexes have emerged as promising photosensitizers for photodynamic therapy, some key drawbacks still hamper clinical translation, such as operability in the phototherapeutic window and reactive oxygen species (ROS) production efficiency and selectivity. In this work, a cyclometalated IrIIIcomplex conjugated to a far‐red‐emitting coumarin, IrIII–COUPY, is reported with highly favourable properties for cancer phototherapy. IrIII–COUPY was efficiently taken up by HeLa cells and showed no dark cytotoxicity and impressive photocytotoxicity indexes after irradiation with green and blue light, even under hypoxia. Importantly, a clear correlation between cell death and intracellular generation of superoxide anion radicals after visible light irradiation was demonstrated. This strategy opens the door to novel fluorescent photodynamic therapy agents with promising applications in theragnosis.
Catalytic Conjunctive Coupling of Carboxylic Acid Derivatives with 9‐BBN‐Derived Ate Complexes
Authors: Law Chunyin , Meng Yan , Koo Seung Moh , Morken James P. 
Published: March 2019

Abstractβ‐Boryl carbonyl compounds are produced by a Ni‐catalyzed cross‐coupling of vinylboron “ate” complexes and acid chloride or acid anhydride electrophiles. The reactions are efficient, being complete in as little as two minutes, and can be applied to a broad range of substrates.
Ligand‐Promoted Iron(III)‐Catalyzed Hydrofluorination of Alkenes
Authors: Xie Yongtao , Sun Peng‐Wei , Li Yuxin , Wang Siwei , Ye Mengchun , Li Zhengming 
Published: March 2019

AbstractAn iron‐catalyzed hydrofluorination of unactivated alkenes has been developed. The use of a multidentate ligand and the fluorination reagent N‐fluorobenzenesulfonimide (NFSI) proved to be critical for this reaction, which afforded various fluorinated compounds in up to 94 % yield.
Absolute Quantification of Noncoding RNA by Microscale Thermophoresis
Authors: Jacob Dominik , Thüring Kathrin , Galliot Aurellia , Marchand Virginie , Galvanin Adeline , Ciftci Akif , Scharmann Karin , Stock Michael , Roignant Jean‐Yves , Leidel Sebastian A. , Motorin Yuri , Schaffrath Raffael , Klassen Roland , Helm Mark 
Published: March 2019

AbstractAccurate quantification of the copy numbers of noncoding RNA has recently emerged as an urgent problem, with impact on fields such as RNA modification research, tissue differentiation, and others. Herein, we present a hybridization‐based approach that uses microscale thermophoresis (MST) as a very fast and highly precise readout to quantify, for example, single tRNA species with a turnaround time of about one hour. We developed MST to quantify the effect of tRNA toxins and of heat stress and RNA modification on single tRNA species. A comparative analysis also revealed significant differences to RNA‐Seq‐based quantification approaches, strongly suggesting a bias due to tRNA modifications in the latter. Further applications include the quantification of rRNA as well as of polyA levels in cellular RNA.
Highly Selective Synthesis of Iridium(III) Metalla[2]catenanes through Component Pre‐Orientation by π⋅⋅⋅π Stacking
Authors: Shan Wei‐Long , Lin Yue‐Jian , Hahn F. Ekkehardt , Jin Guo‐Xin 
Published: March 2019

AbstractA series of molecular metalla[2]catenanes featuring Cp*Ir vertices have been prepared by the template‐free, coordination‐driven self‐assembly of dinuclear iridium acceptors and 1,5‐bis[2‐(4‐pyridyl)ethynyl]anthracene donors. The metalla[2]catenanes were formed by using a strategically selected linker type that is capable of participating in sandwich‐type π–π stacking interactions. In the solid state, the [2]catenanes adopt two different configurations depending on the halogen atoms at the dinuclear metal complex bridge. Altering the solvent or the concentration, as well as the addition of guest molecules, enabled controlled transformations between metalla[2]catenanes and tetranuclear metallarectangles.
Recent Advances in Minisci‐Type Reactions
Authors: Proctor Rupert S. J. , Phipps Robert J. 
Published: March 2019

AbstractReactions that involve the addition of carbon‐centered radicals to basic heteroarenes, followed by formal hydrogen atom loss, have become widely known as Minisci‐type reactions. First developed into a useful synthetic tool in the late 1960s by Minisci, this reaction type has been in constant use over the last half century by chemists seeking to functionalize heterocycles in a rapid and direct manner, avoiding the need for de novo heterocycle synthesis. Whilst the originally developed protocols for radical generation remain in active use today, they have been joined in recent years by a new array of radical generation strategies that allow use of a wider variety of radical precursors that often operate under milder and more benign conditions. The recent surge of interest in new transformations based on free radical reactivity has meant that numerous choices are now available to a synthetic chemist looking to utilize a Minisci‐type reaction. Radical‐generation methods based on photoredox catalysis and electrochemistry have joined approaches which utilize thermal cleavage or the in situ generation of reactive radical precursors. This review will cover the remarkably large body of literature that has appeared on this topic over the last decade in an attempt to provide guidance to the synthetic chemist, as well as a perspective on both the challenges that have been overcome and those that still remain. As well as the logical classification of advances based on the nature of the radical precursor, with which most advances have been concerned, recent advances in control of various selectivity aspects associated with Minisci‐type reactions will also be discussed.
Intermolecular Radical C(sp3)−H Amination under Iodine Catalysis
Authors: Bosnidou Alexandra E. , Muñiz Kilian 
Published: March 2019

AbstractThe direct amination of aliphatic C−H bonds has remained one of the most tantalizing transformations in organic chemistry. Herein, we report on a unique catalyst system, which enables the elusive intermolecular C(sp3)−H amination. This practical synthetic strategy provides access to aminated building blocks and fosters innovative multiple C−H amination within a new approach to aminated heterocycles. The synthetic utility is demonstrated by the synthesis of four relevant pharmaceuticals.
Integration of Graphite and Silicon Anodes for the Commercialization of High‐Energy Lithium‐Ion Batteries
Authors: Chae Sujong , Choi Seong‐Hyeon , Kim Namhyung , Sung Jaekyung , Cho Jaephil 
Published: March 2019

AbstractSilicon is considered a most promising anode material for overcoming the theoretical capacity limit of carbonaceous anodes. The use of nanomethods has led to significant progress being made with Si anodes to address the severe volume change during (de)lithiation. However, less progress has been made in the practical application of Si anodes in commercial lithium‐ion batteries (LIBs). The drastic increase in the energy demands of diverse industries has led to the co‐utilization of Si and graphite resurfacing as a commercially viable method for realizing high energy. Herein, we highlight the necessity for the co‐utilization of graphite and Si for commercialization and discuss the development of graphite/Si anodes. Representative Si anodes used in graphite‐blended electrodes are covered and a variety of strategies for building graphite/Si composites are organized according to their synthetic methods. The criteria for the co‐utilization of graphite and Si are systematically presented. Finally, we provide suggestions for the commercialization of graphite/Si combinations.
Self‐healable and thiol–ene UV‐curable waterborne polyurethane for anticorrosion coating
Authors: Li Ting , Zhang Ze Ping , Rong Min Zhi , Zhang Ming Qiu 
Published: March 2019

ABSTRACTThiol–ene ultraviolet‐curable waterborne polyurethane (WPU) crosslinked networks capable of self‐healing of cracks were developed for anticorrosion coating application. The healing mechanism is attributed to the rearrangement of the crosslinked networks caused by triethylamine‐catalyzed thiol–disulfide exchange reaction proved by high‐performance liquid chromatography, gel permeation chromatography, and rheology tests. The crack remendability can be repeated for at least two times as demonstrated by visual inspection. Moreover, the self‐healing effect was further demonstrated in terms of corrosion and electrochemical tests. Comparatively, the control specimens without disulfide bonds were not self‐healable. The present study provides a simple way for achieving self‐healing WPU to conform to the trend of development of high performance and environmental friendly anticorrosive coatings. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47700.
Toward a large‐scale and deep phenological stage annotation of herbarium specimens: Case studies from temperate, tropical, and equatorial floras
Authors: Lorieul Titouan , Pearson Katelin D. , Ellwood Elizabeth R. , Goëau Hervé , Molino Jean‐Francois , Sweeney Patrick W. , Yost Jennifer M. , Sachs Joel , Mata‐Montero Erick , Nelson Gil , Soltis Pamela S. , Bonnet Pierre , Joly Alexis 
Published: March 2019

Premise of the StudyPhenological annotation models computed on large‐scale herbarium data sets were developed and tested in this study.MethodsHerbarium specimens represent a significant resource with which to study plant phenology. Nevertheless, phenological annotation of herbarium specimens is time‐consuming, requires substantial human investment, and is difficult to mobilize at large taxonomic scales. We created and evaluated new methods based on deep learning techniques to automate annotation of phenological stages and tested these methods on four herbarium data sets representing temperate, tropical, and equatorial American floras.ResultsDeep learning allowed correct detection of fertile material with an accuracy of 96.3%. Accuracy was slightly decreased for finer‐scale information (84.3% for flower and 80.5% for fruit detection).DiscussionThe method described has the potential to allow fine‐grained phenological annotation of herbarium specimens at large ecological scales. Deeper investigation regarding the taxonomic scalability of this approach is needed.