bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulating Protein–Protein Interactions with Visible‐Light‐Responsive Peptide Backbone Photoswitches
Authors: Albert Lea , Peñalver Alberto , Djokovic Nemanja , Werel Laura , Hoffarth Malte , Ruzic Dusan , Xu Jing , Essen Lars‐Oliver , Nikolic Katarina , Dou Yali , Vázquez Olalla 
Published: January 2019

AbstractLife relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function and disease. Modulation of this complex crosstalk has recently attracted attention, even as a novel therapeutic strategy. Herein, we describe the synthesis and characterization of two visible‐light‐responsive peptide backbone photoswitches based on azobenzene derivatives, to exert optical control over protein–protein interactions (PPI). The novel peptidomimetics undergo fast and reversible isomerization with low photochemical fatigue under alternatively blue‐/green‐light irradiation cycles. Both bind in the nanomolar range to the protein of interest. Importantly, the best peptidomimetic displays a clear difference between isomers in its protein‐binding capacity and, in turn, in its potential to inhibit enzymatic activity through PPI disruption. In addition, crystal structure determination, docking and molecular dynamics calculations allow a molecular interpretation and open up new avenues in the design and synthesis of future photoswitchable PPI modulators.
Transesterification of a Tertiary Alcohol by Engineered Candida antarctica Lipase A
Authors: Löfgren Johanna , Görbe Tamás , Oschmann Michael , Svedendahl Humble Maria , Bäckvall Jan‐E. 
Published: January 2019

AbstractTertiary alcohols are known to be challenging substrates for applications in asymmetric synthesis due to their complexity and steric hinderance. The occurrence of tertiary alcohols and their esters in nature indicates the presence of natural biocatalytic synthetic routes for their preparation. Lipase A from Candida antarctica (CalA) is a hydrolase that has previously been shown to catalyze the transesterification of racemic 2‐phenylbut‐3‐yn‐2‐ol at a low rate. In this work, the activity of that enzyme was improved by protein engineering through a semi‐rational design strategy. An enzyme library was created and screened for transesterification activity towards racemic 2‐phenylbut‐3‐yn‐2‐ol in an organic solvent. One successful enzyme variant (L367G) showed a tenfold increased reaction rate compared to the wild‐type enzyme, while maintaining a high enantioselectivity.
Tropolone‐Conjugated DNA: Fluorescence Enhancement in the Duplex
Authors: Bollu Amarnath , Sharma Nagendra K. 
Published: January 2019

AbstractTropolone (2‐hydroxycyclohepta‐2,4,6‐triene‐1‐one and tautomer) is a non‐benzenoid bioactive natural chromophore with pH‐dependent fluorescence character and extraordinary metal binding affinities, especially with transition‐metal ions Cu2+/Zn2+/Ni2+. This report describes the syntheses and biophysical studies of a new tropolonyl thymidine [(4(5)‐hydroxy‐5(4)‐oxo‐5(4)H‐cyclohepta‐1,3,6‐trienyl)thymidine] (tr‐T) nucleoside and of corresponding tropolone‐conjugated DNA oligonucleotides that form B‐form DNA duplex structures with a complementary DNA strand, although their duplex structures are less stable than that of the control. Furthermore, the stabilities of those DNA duplex structures are lowered by the presence of increasing numbers of tr‐T residue or by decreasing pH of their environments. Most importantly, these duplex structures are made fluorescent because of the presence of the tropolone moieties conjugated to the thymidine residues. The fluorescence behavior of those duplex structures exhibits pH dependence, with stronger fluorescence at lower pH and weaker fluorescence at high pH. Importantly, the fluorescence characters of tr‐DNA oligonucleotides are significantly enhanced by nearly threefold after duplex structure formation with their complementary control DNA oligonucleotide. Further, the fluorescence behavior of these tr‐DNA duplex structures is also dependent on the pH conditions. Hence, tropolonyl‐conjugated DNA represents a class of new fluorescent analogues that might be be employed for sensing DNA duplex formation and provide opportunities to improve fluorescence properties further.
Improvements in chemical carriers of proteins and peptides
Authors: Bolhassani Azam 
Published: January 2019

AbstractThe successful intracellular delivery of biologically active proteins and peptides plays an important role for therapeutic applications. Indeed, protein/peptide delivery could overcome some problems of gene therapy, for example, controlling the expression levels and the integration of transgene into the host cell genome. Thus, protein/peptide drug delivery showed a promising and safe approach for treatment of cancer and infectious diseases. Due to the unique physical and chemical properties of proteins, their production (e.g., isolation, purification & formulation) and delivery represented significant challenges in pharmaceutical studies. Modification in the structural moieties of these protein/peptide drugs could improve their solubility, stability, crystallinity, lipophilicity, enzymatic susceptibility and targetability, and subsequently, therapies and cures against various diseases. Using the structural modification of protein/peptide, their delivery provided overall higher success rates including high specificity, high activity, bioreactivity and safety. Recently, biotechnological and pharmaceutical companies have tried to find novel techniques for the modifications and improve delivery systems/carriers. However, each carrier has its own benefits and drawbacks, and an appropriate carrier is often established by the physicochemical properties of protein or peptide, the ideal route of injection, and clinical characteristics of therapy. In this review, an attempt was made to give an overview on the chemical carriers for proteins and peptides as well as the recent advances in this field.
Percutaneous edge‐to‐edge mitral valve repair may rescue select patients in cardiogenic shock: Findings from a single center case series
Authors: Flint Kelsey , Brieke Andreas , Wiktor Dominik , Carroll John 
Published: January 2019

AbstractBackgroundPatients with severe mitral regurgitation (MR) and cardiogenic shock are typically too high risk for immediate surgery; however, percutaneous edge‐to‐edge mitral valve repair (pMVr) may be reasonable in select patients.AimDescribe characteristics and outcomes of patients who underwent pMVr with and without shock at a single center.MethodsChart review of all patients who underwent non‐investigational pMVr from November 2013 to October 2018. Shock was defined as dependence on an intravenous (IV) inotrope, IV afterload reduction, and/or temporary mechanical circulatory support immediately preceding pMVr.ResultsThere were 135 patients. Mean age was 80 ± 12 years and 56 (41%) were female. Twelve (8.9%) had shock. All patients had 3+ or 4+ MR at baseline. Post‐procedure, all shock patients had 2+ or less MR. Two (17%) shock patients and 4 (3%) non‐shock patients died within 30 days of pMVr (P = 0.03). Six (50%) shock patients had resolution of shock and discharged home (primary outcome). Five shock patients had acute MI, four of whom met the primary outcome. Four shock patients had chronic MR (>21 days), three of whom did not meet the primary outcome. Overall, follow‐up time for mortality was median (IQR) 198 (42–379) days. Shock patients who survived to 30 days post‐procedure had significantly shorter time from diagnosis of MR to pMVr compared to those who died (35 ± 68 vs. 374 ± 111 days; P = 0.0001).ConclusionPercutaneous edge‐to‐edge MVr may be reasonable in shock patients with acute MR and/or acute MI. This case series should guide larger studies designed to improve selection of shock patients for pMVr.
Effect of Glu‐D1 gene introgression and amylose content on breadmaking potential of blends of durum and hexaploid wheat
Authors: Sissons Mike , Pleming Denise , Sestili Francesco , Lafiandra Domenico 
Published: January 2019

AbstractBackground and objectivesDurum wheat is used to make leavened bread; however, durum bread has inferior loaf volume, structure, and texture compared to bread made from common wheat. One approach to overcome this is to transfer key storage protein genes present at the Glu‐D1 locus from bread wheat into durum. Durum wheat Svevo missing Glu‐B1subunits 7 + 8 and Lira biotypes with low molecular weight glutenin subunits types 1 and 2 were evaluated for their breadmaking potential with and without high molecular weight glutenin subunits 2 + 12 or 5 + 10.FindingsBread made from blends of durum and a commercial baker's flour (10%, 25%, 50% w/w) assessed over two seasons in 10 different genotypes showed that as more durum was included in the mixture, loaf volume and texture score declined. Incorporation of the 2 + 12 subunit pair in the genotypes Lira42 and Lira45 improved bread quality but not in Svevo, whereas including 5 + 10 improved bread quality of Lira42 had no effect on Lira45 but reduced quality of Svevo. Low amylose Svevo had similar loaf quality to Svevo while adding 5 + 10 had minimal impact except at 50% with a small improvement in loaf quality. Bread stored up to 7 days became firmer partly due to increased starch retrogradation, and loaves were similar to bread made from baker's flour. Low amylose Svevo kept the loaf fresher but only up to 3 days of storage. Subunit pair 5 + 10 made the loaf firmer after 7 days compared to control.ConclusionsAddition of the 2 + 12 or 5 + 10 benefited the weaker type gluten as found in Lira 42 (LMW‐1, HMW 20) but not with stronger dough in Svevo even in the absence of HMW 7 + 8. It appears that while Glu‐D1 subunits are critical for good breadmaking in hexaploid wheat, they appear to have limited value in improving loaf volume and structure in durum bread.Significance and noveltySome improvements in bread quality can be obtained by introducing genes coding for Glu‐D1subunits 2 + 12 and 5 + 10 in durum wheat depending on the genotype, especially weak dough types, and the results presented comprise the first report of such effect.
W/O/W Multiple Emulsions as the Functional Component of Dairy Products
Authors: Klojdová Iveta , Štětina Jiří , Horáčková Šárka 
Published: January 2019

AbstractWater‐in‐oil‐in‐water (w/o/w) multiple emulsions are considered that could be suitable components of functional dairy products. Such emulsions enable the preparation of low‐calorie products, encapsulation of bioactive components or microorganisms, and their protection during digestion. Because of the large phase interface, w/o/w emulsions are thermodynamically unstable. Therefore, their preparation and stabilization requires specific conditions. This review describes a potential industrial application of w/o/w emulsions in dairy products in detail and summarizes the value, preparation, stabilization, and evaluation of w/o/w emulsions in a dairy system.
Core‐Shell Structure of SnO2@C/PEDOT : PSS Microspheres with Dual Protection Layers for Enhanced Lithium Storage Performance
Authors: Li Hui , Zhang Bao , Ou Xing , Zhou Qijie , Wang Chunhui , Peng Chunli , Zhang Jiafeng 
Published: January 2019

AbstractAbundant material SnO2 is considered as a promising lithium‐ion battery (LIB) anode candidate due to its high theoretical capacity. Yet, the achieved capacity is restricted by the severe cycling degradation. Rational structural design can mitigate the volume expansion of SnO2, improving the structural stability and reaction kinetics at the same time. Herein, core‐shell structured SnO2@C/PEDOT : PSS microspheres are synthesized through a facile approach combined with hydrothermal treatment and polymerization. In the well‐designed architecture, amorphous carbon coated ultrafine SnO2 nanoparticles are aggregated into regular microspheres and wrapped by a PEDOT : PSS layer, forming a robust core‐shell structure with dual protection layers. Such hierarchical structure provides sufficient ion/electron ingress/transport channels, restrains the adverse reaction of the electrolyte, improves the conductivity and buffers the interior stress of the entire electrode, resulting in the stable cycle performance. When evaluated as LIB anode, it demonstrates an initial reversible capacity of 1170.5 mAh g−1 at 0.1 C, maintaining a high capacity of 441.5 mAh g−1 after 1200 stable cycles at high rate of 2 C. The strategy gives a rational avenue to design the oxide anodes with efficient hierarchical structure for LIB development.
Bio‐Electrosynthesis of Vectorially Imprinted Polymer Nanofilms for Cytochrome P450cam
Authors: Jetzschmann Katharina J. , Tank Steffen , Jágerszki Gyula , Gyurcsányi Róbert E. , Wollenberger Ulla , Scheller Frieder W. 
Published: January 2019

AbstractA new approach for synthesizing a “vectorially” imprinted polymer (VIP) is presented for the microbial cytochrome P450cam enzyme. A surface attached binding motif of a natural reaction partner of the target protein, putidaredoxin (Pdx), is the anchor to the underlying transducer. The 15 amino acid peptide anchor, which stems from the largest continuous amino acid chain within the binding site of Pdx was modified: (i) internal cysteines were replaced by serines to prevent disulfide bond formation; (ii) 2 ethylene glycol units were attached to the N‐terminus as a spacer region; and (iii) an N‐terminal cysteine was added to allow the immobilization on the gold electrode surface. Immobilization on GCE was achieved via an N‐(1‐pyrenyl)maleimide (NPM) cross‐linker. In this way oriented immobilization of P450cam was accomplished by binding it to a peptide‐modified gold or glassy carbon electrode (GCE) prior to the electrosynthesis of a polymer nanofilm around the immobilized target. This VIP nanofilm enabled reversible oriented docking of P450cam as it is indicated by the catalytic oxygen reduction via direct electron transfer between the enzyme and the underlying electrode. Catalysis of oxygen reduction by P450cam bound to the VIP‐modified GCE was used to measure rebinding to the VIP. The “mild” coupling of an oxidoreductase with the electrode may be appropriate for realizing electrode‐driven substrate conversion by instable P450 enzymes without the need of NADPH co‐factor.
Intramolecular Energy Transfer in Dithienogermole Derivatives
Authors: Adachi Yohei , Nomura Takanori , Ohshita Joji 
Published: January 2019

AbstractDithienogermole (DTG) has been applied as a useful building unit of optical/semiconducting materials for organic optoelectronic devices because of its extended conjugation, high chemical stability, and good emissive properties. Although DTG has two substituents on the Ge atom, the substituents have been limited to simple alkyl and aryl groups in previous work. In this work, to further uncover the new functionalities of this useful building unit, various π‐conjugated groups were introduced on Ge of DTG. It was expected that the introduction of π‐conjugated groups would give rise to efficient energy transfer between the substituents and the DTG core, which are in proximity and linked by a Ge atom. The thus‐prepared DTG compounds with fluorene, terthiophene, and pyrene units on Ge possessed well‐separated frontier orbitals on the substituents and the DTG core, as proved by the absorption spectra and DFT calculations. The substituted DTG derivatives showed clear emission only from the energy acceptor even though the energy donor was photoexcited. This indicated the highly efficient energy transfer in these compounds. We also prepared more π‐extended compound DTGFl2‐Ph with phenyl groups on the DTG thiophene rings. DTGFl2‐Ph showed strong emission in the visible region with efficient energy transfer properties. These results clearly indicate the potential application of the present DTG system as optical functional materials.
Harnessing Brightness in Naphthalene Diimides
Authors: Maniam Subashani , Higginbotham Heather F. , Bell Toby D. M. , Langford Steven J. 
Published: January 2019

AbstractThe development of brightly emissive compounds is of great research and commercial interest, with established and emerging applications across chemistry, biology, physics, medicine and engineering. Among the many types of molecules available, naphthalene diimides have been widely used for both fundamental photophysical studies and in practical applications that utilise fluorescence as an information readout. The monomeric naphthalene diimide is weakly fluorescent, however through various methods of core‐derivatisation, it can be developed to be highly fluorescent and further functionalised to add utility. In this review, we highlight recent advances made in naphthalene diimide chemistry that have led to development of molecules with improved optical properties, and the design strategies utilised to produce bright fluorescence emission as small molecules or in supramolecular architectures.
π‐Concave Hosts for Curved Carbon Nanomaterials
Authors: Selmani Serxho , Schipper Derek J. 
Published: January 2019

AbstractCarbon nanomaterials have been at the forefront of nanotechnology since its inception. At the heart of this research are the curved carbon nanomaterial families: fullerenes and carbon nanotubes. While both have incredible properties that have been capitalized upon in a wide variety of applications, there is an aspect that is not commonly exploited by nanoscientists and organic chemists alike: the interaction of curved carbon nanomaterials with curved organic small molecules. By taking advantage of these interactions, new avenues are opened for the use of fullerenes and carbon nanotubes.
Enantioselective liquid‐liquid extraction of DL‐mandelic acid using chiral diphosphine ligands as extractants
Authors: Ma Yu , Liu Xiong , Zhou Wenqi , Cao Ting 
Published: January 2019

AbstractIn order to expand the application range of chiral diphosphine ligands, (S)‐BINAP, (S)‐SEGPHOS, and (S)‐MeO‐BIPHEP were employed as extractants to recognize DL‐mandelic acid. The results indicated that (S)‐SEGPHOS‐Cu exhibited considerable ability to recognize DL‐mandelic acid with operational enantioselectivity (α) of 2.677. The process of extraction of DL‐mandelic acid using (S)‐SEGPHOS‐Cu as extractant was systematically investigated. Performance factor (pf) was adopted to comprehensively evaluate the extraction. After optimization by response surface methodology (RSM), the optimal extraction condition is temperature of 5.5°C, (S)‐SEGPHOS‐Cu concentration of 3.0 mmol/L, and pH of 8.0. And the predicted and experimental maximum values of pf were 0.26374 and 0.26839, respectively.
Synthesis of Alumina‐Coated Natural Graphite for Highly Cycling Stability and Safety of Li‐Ion Batteries
Authors: Xu Tao , Zhou Chengkun , Zhou Haihui , Wang Zekun , Ren Jianguo 
Published: January 2019

Summary of main observation and conclusionThe natural graphite (NG) uniformly coated with alumina ceramics (Al2O3) was successfully synthesized through sol‐gel method. The aluminum plastic film soft‐packed battery prepared using Al2O3‐coated NG as anode material exhibits excellent cycle performance and safety performance. The cycling retention of AN‐1 is 84.95% after 200 cycles at a rate of 1 C in a potential window ranging from 3.0 to 4.35 V, which is much greater than 75.07% of NG under the same test conditions. The result of the nail penetration tests shows that the successful nail penetration rate of the NG used as anode is 0%, while that of Al2O3 coated samples AN‐1 is 100%. The test results show that the Al2O3 coating could act as a solid electrolyte to suppress side reactions, improve cycle stability, and prevent a thermal runaway under mechanical abuse.
Reducing plastic waste – experiments with insects and enzymes
Authors: Müller Sarah Christin , Heimann Rebekka 
Published: January 2019

AbstractIm Rahmen dieses Beitrags werden drei Experimente beschrieben, mit denen neuere Ansätze zur Reduzierung des Kunststoffmülls im Chemieunterricht und im fächerübergreifenden Unterricht erarbeitet werden können. Mögliche Schlussfolgerungen aus den experimentellen Ergebnissen und Aussagegrenzen können mit den Schülerinnen und Schülern kritisch diskutiert werden.
Discovery of N‐Aryloxypropylbenzylamines as Voltage‐Gated Sodium Channel NaV1.2‐Subtype‐Selective Inhibitors
Authors: van der Peet Phillip L. , Sandanayake Saman , Jarrott Bevyn , Williams Spencer J. 
Published: January 2019

AbstractWe previously reported that a lipophilic N‐(4′‐hydroxy‐3′,5′‐di‐tert‐butylbenzyl) derivative (1) of the voltage‐gated sodium channel blocker mexiletine, was a more potent sodium channel blocker in vitro and in vivo. We demonstrate that replacing the chiral methylethylene linker between the amine and di‐tert‐butylphenol with an achiral 1,3‐propylene linker (to give (2)) maintains potency in vitro. We synthesized 25 analogues bearing the 1,3‐propylene linker and found that minor structural changes resulted in pronounced changes in state dependence of blocking human NaV1.2 and 1.6 channels by high‐throughput patch‐clamp analysis. Compared to mexiletine, compounds 1 and 2 are highly selective NaV1.2 inhibitors and >500 times less potent in inhibiting NaV1.6 channels. On the other hand, a derivative (compound 4) bearing 2,6‐dimethoxy groups in place of the 2,6‐dimethyl groups found in mexiletine was found to be the most potent inhibitor, but is nonselective against both channels in the tonic, frequency‐dependent and inactivated states. In a kindled mouse model of refractory epilepsy, compound 2 inhibited seizures induced by 6 Hz 44 mA electrical stimulation with an IC50 value of 49.9±1.6 mg kg−1. As established sodium channel blockers do not suppress seizures in this mouse model, this indicates that 2 could be a promising candidate for treating pharmaco‐resistant epilepsy.
Influence of Renal Function on Evolocumab Exposure, Pharmacodynamics, and Safety
Authors: Lee Edward , Gibbs John P. , Emery Maurice G. , Block Geoffrey , Wasserman Scott M. , Hamilton Lisa , Kasichayanula Sreeneeranj , Hanafin Patrick , Somaratne Ransi , Egbuna Ogo 
Published: January 2019

AbstractWe evaluated the pharmacokinetics, pharmacodynamics, and safety of evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), in an open‐label, parallel‐design study in participants with normal renal function (n = 6), severe renal impairment (RI; n = 6), or end‐stage renal disease (ESRD) receiving hemodialysis (n = 6) who received a single 140‐mg dose of evolocumab. The effects of evolocumab treatment on low‐density lipoprotein cholesterol (LDL‐C) lowering and unbound PCSK9 concentrations were similar in the normal renal function group and the renally impaired groups. Geometric mean Cmax and AUClast values in the severe RI and ESRD hemodialysis groups compared with the normal renal function group were lower but within 37% of the normal renal function group (Jonckheere‐Terpstra trend test; Cmax, P = .23; AUClast, P = .22) and within 26% after adjusting for body weight (mean body weight was approximately 9% higher in the renally impaired groups compared with the normal renal function group). No correlations were observed between exposure and baseline creatinine clearance. No adverse event was determined by the investigators to be related to evolocumab, and there were no trends indicative of clinically important effects on laboratory variables or vital signs. Overall, there were no meaningful differences in evolocumab exposure, as assessed by Cmax and AUClast, in patients with severe RI and ESRD hemodialysis compared with patients with normal renal function, and LDL‐C‐lowering effects were similar across groups. These results support the use of evolocumab without dose adjustment in patients who have severe RI or ESRD.