bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macrocyclic Bis(phenanthroline‐pyrrole): A Convenient One‐Pot Synthesis, Structure(s), Spectroscopic, and Redox Properties, and the Binding of Amine Guests, Protons, and Lanthanide Ions
Authors: McSkimming Alex , Shrestha Sumi , Bhadbhade Mohan M. , Thordarson Pall , Colbran Stephen B. 
Published: October 2013

AbstractThis paper reports a convenient, one‐pot, easily scalable and readily modifiable synthesis of a novel large‐ring bis(1,10‐phenanthrolinyl‐2,5‐pyrrole) macrocycle, H2LMC and describes its spectroscopic and electrochemical properties, protonation, cooperative amine binding, electrocatalysis of the oxidation of primary amines, photosensitization of the decomposition of dichloromethane, and the first lanthanide complexes of the hexaaza‐dianion LMC2− including the novel dimer, [(NO3)(LMC)Eu(μ‐OH)Eu(LMC)(H2O)2]⋅2py.
Chitosan‐Capped Mesoporous Silica Nanoparticles as pH‐Responsive Nanocarriers for Controlled Drug Release
Authors: Hu Xiaoxi , Wang Yun , Peng Bo 
Published: October 2013

AbstractHerein, we present a straightforward synthesis of pH‐responsive chitosan‐capped mesoporous silica nanoparticles (MSNs). These MCM‐41‐type MSNs could be used as nanocapsules to accommodate guest molecules. Subsequently, (3‐glycidyloxypropyl)trimethoxysilane was grafted onto the surface of the MSNs, which served as a bridge to link between MSNs and chitosan, which is ubiquitous in nature and commercially available. Owing to the pH‐responsive and biocompatible features of chitosan, the loading and release of an anti‐cancer drug, doxorubicin hydrochloride, were carried out in vitro, in which the composite chitosan‐capped MSNs (CS‐MSNs) showed excellent environmental response. As the pH value of the media decreased, the degree of drug release correspondingly increased. Moreover, thanks to the perfect biocompatibility of chitosan, the CS‐MSNs exhibited lower cytotoxicity than that of the naked MSNs in an MTT assay. In addition, the in vitro kill potency against MCF‐7 breast‐cancer cells was enhanced over time, as well as with increasing concentration of the drug‐loaded CS‐MSNs. These results indicate that CS‐MSNs are promising candidates for pH‐responsive drug delivery in cancer therapy.
Discovery and Biological Characterization of the Auromomycin Chromophore as an Inhibitor of Biofilm Formation in Vibrio cholerae
Authors: Peach Kelly C. , Cheng Andrew T. , Oliver Allen G. , Yildiz Fitnat H. , Linington Roger G. 
Published: October 2013

AbstractBacterial biofilms pose a significant challenge in clinical environments due to their inherent lack of susceptibility to antibiotic treatment. It is widely recognized that most pathogenic bacterial strains in the clinical setting persist in the biofilm state, and are the root cause of many recrudescent infections. The discovery and development of compounds capable of either inhibiting biofilm formation or initiating biofilm dispersal might provide new therapeutic avenues for reducing the number of hospital‐acquired, biofilm‐mediated infections. We detail here the application of our recently reported image‐based, high‐throughput screen to the discovery of microbially derived natural products with inhibitory activity against Vibrio cholerae biofilm. Examination of a prefractionated library of microbially derived marine natural products has led to the identification of a new biofilm inhibitor that is structurally unrelated to previously reported inhibitors and is one of the most potent inhibitors of V. cholerae reported to date. Combination of this compound with sub‐MIC concentrations of a number of clinically relevant antibiotics was shown to improve the inhibitory efficacy of this new compound compared to monotherapy treatments, and provides evidence for the potential therapeutic benefit of biofilm inhibitors in treating persistent biofilm‐mediated infections.
Base‐Pairing Behavior of a Carbocyclic Janus‐AT Nucleoside Analogue Capable of Recognizing A and T within a DNA Duplex
Authors: Largy Eric , Liu Wenbo , Hasan Abid , Perrin David M. 
Published: October 2013

AbstractJanus‐type nucleosides are heterocycles with two faces, each of which is designed to complement the H‐bonding interactions of natural nucleosides comprising a canonical Watson–Crick base pair. By intercepting all of the hydrogen bonds contained within the base pair, oligomeric Janus nucleosides are expected to achieve sequence‐specific DNA recognition through the formation of J‐loops that will be more stable than D‐loops, which simply replaces one base‐pair with another. Herein, we report the synthesis of a novel Janus‐AT nucleoside analogue, JAT, affixed on a carbocyclic analogue of deoxyribose that was converted to the corresponding phosphoramidite. A single JAT was successfully incorporated into a DNA strand by solid phase for targeting both A and T bases, and characterized through biophysical and computational methods. Experimental UV‐melting and circular dichroism data demonstrated that within the context of a standard duplex, JAT associates preferentially with T over A, and much more poorly with C and G. Density functional theory calculations confirm that the JAT structure is well suited to associate only with A and T thereby highlighting the importance of the electronic structure in terms of H‐bonding. Finally, molecular dynamics simulations validated the observation that JAT can substitute more effectively as an A‐analogue than as a T‐analogue without substantial distortion of the B‐helix. Overall, this new Janus nucleotide is a promising tool for the targeting of A–T base pairs in DNA, and will lead to the development of oligo‐Janus‐nucleotide strands for sequence‐specific DNA recognition.
Ribosomal Protein S5e is Implicated in Translation Initiation through its Interaction with the N‐Terminal Domain of Initiation Factor eIF2α
Authors: Sharifulin Dmitri , Babaylova Elena , Kossinova Olga , Bartuli Yulia , Graifer Dmitri , Karpova Galina 
Published: October 2013

AbstractA key step of translation initiation in eukaryotes is formation of the 48S preinitiation complex (PIC) containing the 40S ribosome, a set of eukaryotic initiation factors (eIFs), mRNA, and initiator Met‐tRNA interacting with mRNA start codon; however, the PIC structure remains substantially unknown. Here, we apply formaldehyde‐induced protein–protein crosslinks to identify contacts between ribosomal protein S5e (rpS5e, “e” stands for “eukaryotic”) and eIFs within the mammalian PIC, assembled on either model canonical or IRES‐containing mRNA. Using immunoblotting and mass spectrometry, we show that with both types of mRNA, rpS5e crosslinks to eIF2α. Comparative analysis of peptides resulting from trypsinolysis of the crosslinked proteins before and after crosslink reversal reveals crosslinked peptides in the N‐terminal parts of rpS5e and eIF2α. Application of these data to a model PIC structure obtained with the use of available structures indicates that eIF2α undergoes major conformation rearrangements to enable contacts of the factor with rpS5e. These contacts are suggested to maintain the correct positioning of eIF2α relative to other PIC components; this could be essential for start‐codon selection by the PIC.
Bicyclic Peptide Inhibitor of Urokinase‐Type Plasminogen Activator: Mode of Action
Authors: Roodbeen Renée , Paaske Berit , Jiang Longguang , Jensen Jan K. , Christensen Anni , Nielsen Jakob T. , Huang Mingdong , Mulder Frans A. A. , Nielsen Niels Chr. , Andreasen Peter A. , Jensen Knud J. 
Published: October 2013

AbstractThe development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptide‐based inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase‐type plasminogen activator (uPA), based on the established monocyclic peptide, upain‐2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across‐the‐ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain‐2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain‐2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also investigated the solution structures of the bicyclic peptide by NMR spectroscopy to map possible conformations. An X‐ray structure of the bicyclic‐peptide–uPA complex confirmed an interaction similar to that for the previous upain‐1/upain‐2–uPA complexes. These physical studies of the peptide–protease interactions will aid future designs of bicyclic peptide protease inhibitors.
Effects of Charge and Charge Distribution on the Cellular Uptake of Multivalent Arginine‐Containing Peptide–Polymer Conjugates
Authors: Koschek Katharina , Dathe Margitta , Rademann Jörg 
Published: October 2013

AbstractCopolymers of N‐(2‐hydroxypropyl)methacrylamide (HPMA) and N‐methacryloyl‐β‐alaninyl‐S‐benzyl thioester were prepared by employing free radical or RAFT conditions and denominated as “NCL polymers”. The copolymer with a polydispersity index of 1.2–1.3 was used for the direct conjugation of unprotected peptides and peptide mixtures bearing differentially loaded side chains by native chemical ligation reactions conducted in aqueous buffer. Uptake into human HeLa cells was correlated with the overall surface charge and the ζ potentials of the peptide–polymer conjugates. Most notable were the differential effects found for various multivalent peptide–polymer conjugates containing arginine residues. Although positive ζ potentials were required for cellular uptake of the peptide–polymer conjugates, this sole charge effect was strongly dominated by the effect exerted by the relative distribution of arginine residues. Polymers conjugated with nona‐arginine peptides were over‐proportionally taken up, relative to their surface charge, compared to polymers with random distribution of single arginine residues. In view of these findings, peptide–polymer compositions suitable for efficient cellular uptake with negligible toxicity at polymer concentrations relevant for intracellular functional studies were determined.
A Single Mutation at the Ferredoxin Binding Site of P450 Vdh Enables Efficient Biocatalytic Production of 25‐Hydroxyvitamin D3
Authors: Yasutake Yoshiaki , Nishioka Taiki , Imoto Noriko , Tamura Tomohiro 
Published: October 2013

AbstractVitamin D3 hydroxylase (Vdh) from Pseudonocardia autotrophica is a cytochrome P450 monooxygenase that catalyzes the two‐step hydroxylation of vitamin D3 (VD3) to produce 25‐hydroxyvitamin D3 (25(OH)VD3) and 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2VD3). These hydroxylated forms of VD3 are useful as pharmaceuticals for the treatment of conditions associated with VD3 deficiency and VD3 metabolic disorder. Herein, we describe the creation of a highly active T107A mutant of Vdh by engineering the putative ferredoxin‐binding site. Crystallographic and kinetic analyses indicate that the T107A mutation results in conformational change from an open to a closed state, thereby increasing the binding affinity with ferredoxin. We also report the efficient biocatalytic synthesis of 25(OH)VD3, a promising intermediate for the synthesis of various hydroxylated VD3 derivatives, by using nisin‐treated Rhodococcus erythropolis cells containing VdhT107A. The gene‐expression cassette encoding Bacillus megaterium glucose dehydrogenase‐IV was inserted into the R. erythropolis chromosome and expressed to avoid exhaustion of NADH in a cytoplasm during bioconversion. As a result, approximately 573 μg mL−1 25(OH)VD3 was successfully produced by a 2 h bioconversion.
Mycobacterial Phenolic Glycolipids with a Simplified Lipid Aglycone Modulate Cytokine Levels through Toll‐Like Receptor 2
Authors: Elsaidi Hassan R. H. , Barreda Daniel R. , Cairo Christopher W. , Lowary Todd L. 
Published: October 2013

AbstractPhenolic glycolipids (PGLs) are virulence factors present in the cell walls of many pathogenic mycobacteria. PGLs have been implicated in various aspects of mycobacterial disease, but there are limited structure–activity data available for these molecules. We report here the preparation of seven synthetic PGL analogues, differing from the native compounds in the replacement of the complex phenolic lipid moiety with a p‐methoxyphenyl group. The ability of these compounds to stimulate or inhibit the production of cytokines (TNF‐α, IL‐1β, IL‐6, MCP‐1) and nitric oxide (NO) was then evaluated by ELISA‐based assays. None of the compounds stimulated the production of these biological signalling molecules. In contrast, they each displayed concentration‐dependent inhibitory activity, related to the methylation pattern of the molecule and mediated by Toll‐like receptor 2. Additional studies revealed that native PGL‐I from Mycobacterium leprae and a synthetic PGL‐I analogue containing a simplified lipid domain had enhanced inhibitory activities relative to the corresponding analogues containing the p‐methoxyphenyl aglycone; however, the natural lipid phenolthiocerol was only weakly active. These studies reveal that synthetic molecules of this type can be used as probes for PGL function. Moreover, their ease of synthesis relative to the natural glycolipids, as well as their more favourable aqueous solubility, should allow for more thorough structure–activity relationship studies.
Position of Cu Atoms at the Pt(111) Electrode Surfaces Controls Electrosorption of (H)SO4(2)− from H2SO4 Electrolytes
Authors: Tymoczko Jakub , Schuhmann Wolfgang , Bandarenka Aliaksandr S. 
Published: October 2013

AbstractSelective positioning of monolayer amounts of foreign atoms at the surface and subsurface regions of metal electrodes is a promising way to fine‐tune the properties of the electrode/electrolyte interface. The latter is critical as it largely governs the adsorption of electrolyte components and reaction intermediates and, therefore, controls many key electrocatalytic processes. Using model Pt(111) single‐crystal electrodes, we demonstrate how the relative position of Cu atoms at the surface drastically changes the adsorption energies for (bi)sulfate anions. Our measurements involve pseudomorphic overlayers of Cu on Pt(111) as well as Cu–Pt(111) surface and sub‐surface alloys, where Cu atoms were located either in the first or in the second atomic layers of Pt, respectively. In the case of Cu–Pt(111) surface alloys, specific adsorption of the anions starts earlier compared to the unmodified Pt(111) surface. In contrast, placing Cu atoms into the second atomic layer weakens the binding between the surface and the anions. Surprisingly, Cu pseudomorphic overlayers do not reveal any specific adsorption of (bi)sulfates (within the region of the overlayer stability). Taking into account that electrified interfaces between Pt(111) electrodes and sulfate‐containing electrolytes often play the role of benchmark systems in fundamental physico‐chemical and, particularly, electrocatalytic studies, our findings demonstrate a promising and relatively easy route of tuning the properties of these interfaces.
The Formation and Role of Oxide Layers on Pt during Hydrazine Oxidation in Protic Ionic Liquids
Authors: Walsh Darren A. , Ejigu Andinet , Muhammad Sayyar , Licence Peter 
Published: October 2013

AbstractThe electrochemistry of platinum is studied in the protic ionic liquids dimethylethylammonium trifluoromethanesulfonate, diethylmethylammonium trifluoromethanesulfonate and diethylmethylammonium bis(trifluoromethanesulfonyl)imide. Oxide layers form on platinum due to trace water oxidation in the ionic liquids at potentials of about 1.0 V and the oxide growth kinetics change as the potential increases Above 60 °C, multilayers of oxide form in each ionic liquid at high potentials. The hydrazine oxidation reaction was used as a probe of the reactivity of the oxide layers and significant differences in the behaviour of the [TfO]−‐based ionic liquids and [dema][Tf2N] are observed during hydrazine oxidation. Specifically, significant “activation” of the Pt electrode towards hydrazine oxidation is observed in the [TfO]−‐based liquids whereas the electrode appears to be poisoned rapidly in [dema][Tf2N]. The electrochemically formed oxide layers are sensitive to the presence of hydrazine dissolved in dimethylethylammonium trifluoromethanesulfonate and immersion of the “activated” oxide‐coated Pt in a hydrazine/ionic liquid solution for extended periods of time results in deactivation of the platinum surface.
Biotin‐Labeled Electropolymerized Network of Gold Nanoparticles for Amperometric Immunodetection of Human Fibrinogen
Authors: Díez Paula , Gamella María , Martínez‐Ruíz Paloma , Lanzone Valentina , Sánchez Alfredo , Sánchez Enrique , Garcinuño Belit , Villalonga Reynaldo , Pingarrón José M. 
Published: October 2013

AbstractWater‐soluble gold nanoparticles (3.1±0.6 nm) with polymerization ability and affinity to streptavidin are prepared by reducing HAuCl4 in the presence of the capping ligands 2‐mercaptoethanesulfonic acid, biotin–cysteamine, and p‐aminothiophenol. This colloid, HAuCl4, is used to modify gold electrodes by forming a 3D electropolymerized network of bis‐aniline‐cross‐linked nanoparticles on the metal surface. The modified electrode is used as a scaffold for the assembly of an amperometric immunosensor system to detect human fibrinogen. The immunosensor shows excellent analytical characteristics, with a dynamic range of detection between 0.018 and 2.208 μg mL−1, a detection limit of 4 ng mL−1, and a half‐maximal inhibitory concentration (IC50) of 177 ng mL−1. The immunosensor is markedly stable, retaining full analytical capacity after 45 days of storage at 4 °C.
Probing Binding and Cellular Activity of Pyrrolidinone and Piperidinone Small Molecules Targeting the Urokinase Receptor
Authors: Mani Timmy , Liu Degang , Zhou Donghui , Li Liwei , Knabe William Eric , Wang Fang , Oh Kyungsoo , Meroueh Samy O. 
Published: October 2013

AbstractThe urokinase receptor (uPAR) is a cell‐surface protein that is part of an intricate web of transient and tight protein interactions that promote cancer cell invasion and metastasis. Here, we evaluate the binding and biological activity of a new class of pyrrolidinone and piperidinone compounds, along with derivatives of previously‐identified pyrazole and propylamine compounds. Competition assays revealed that the compounds displace a fluorescently labeled peptide (AE147‐FAM) with inhibition constant (Ki) values ranging from 6 to 63 μM. Structure‐based computational pharmacophore analysis followed by extensive explicit‐solvent molecular dynamics (MD) simulations and free energy calculations suggested the pyrazole‐based and piperidinone‐based compounds adopt different binding modes, despite their similar two‐dimensional structures. In cells, pyrazole‐based compounds showed significant inhibition of breast adenocarcinoma (MDA‐MB‐231) and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but piperidinone‐containing compounds exhibited no cytotoxicity even at concentrations of 100 μM. One pyrazole‐based compound impaired MDA‐MB‐231 invasion, adhesion, and migration in a concentration‐dependent manner, while the piperidinone inhibited only invasion. The pyrazole derivative inhibited matrix metalloprotease‐9 (gelatinase) activity in a concentration‐dependent manner, while the piperidinone showed no effect suggesting different mechanisms for inhibition of cell invasion. Signaling studies further highlighted these differences, showing that pyrazole compounds completely inhibited ERK phosphorylation and impaired HIF1α and NF‐κB signaling, while pyrrolidinones and piperidinones had no effect. Annexin V staining suggested that the effect of the pyrazole‐based compound on proliferation was due to cell killing through an apoptotic mechanism. The compounds identified represent valuable leads in the design of further derivatives with higher affinities and potential probes to unravel the protein–protein interactions of uPAR.
Selective Adsorption of Functionalized Nanoparticles to Patterned Polymer Brush Surfaces and Its Probing with an Optical Trap
Authors: Steinbach Annina , Paust Tobias , Pluntke Manuela , Marti Othmar , Volkmer Dirk 
Published: October 2013

AbstractThe site‐specific attachment of nanoparticles is of interest for biomaterials or biosensor applications. Polymer brushes can be used to regulate this adsorption, so the conditions for selective adsorption of phosphonate‐functionalized nanoparticles onto micropatterned polymer brushes with different functional groups are optimized. By choosing the strong polyelectrolytes poly(3‐sulfopropyl methacrylate), poly(sulfobetaine methacrylate), and poly[2‐(methacryloyloxy)ethyl trimethylammonium chloride], it is possible to direct the adsorption of nanoparticles to specific regions of the patterned substrates. A pH‐dependent adsorption can be achieved by using the polycarboxylate brush poly(methacrylic acid) (PMAA) as substrate coating. On PMAA brushes, the nanoparticles switch from attachment to the brush regions to attachment to the grooves of a patterned substrate on changing the pH from 3 to 7. In this manner, patterned substrates are realized that assemble nanoparticles in pattern grooves, in polymer brush areas, or substrates that resist the deposition of the nanoparticles. The nanoparticle deposition can be directed in a pH‐dependent manner on a weak polyelectrolyte, or is solely charge‐dependent on strong polyelectrolytes. These results are correlated with surface potential measurements and show that an optical trap is a versatile method to directly probe interactions between nanoparticles and polymer brushes. A model for these interactions is proposed based on the optical trap measurements.
Structural and Magnetic Properties of 3d Transition‐Metal‐Atom Adsorption on Perfect and Defective Graphene: A Density Functional Theory Study
Authors: Zhang Tingting , Zhu Liyan , Yuan Shijun , Wang Jinlan 
Published: October 2013

AbstractWe systematically investigate the interactions and magnetic properties of a series of 3d transition‐metal (TM; Sc–Ni) atoms adsorbed on perfect graphene (G6), and on defective graphene with a single pentagon (G5), a single heptagon (G7), or a pentagon–heptagon pair (G57) by means of spin‐polarized density functional calculations. The TM atoms tend to adsorb at hollow sites of the perfect and defective graphene, except for G6Cr, G5Cr, and G5Ni. The binding energies of TMs on defective graphene are remarkably enhanced and show a V‐shape, with GNCr and GNMn having the lowest binding energies. Furthermore, complicated element‐ and defect‐dependent magnetic behavior is observed in GNTM. Particularly, the magnetic moments of GNTM linearly increase by about 1 μB and follow a hierarchy of G7TM<G57TM<G5TM as the TM varies from Sc to Mn, and the magnetic moments begin to decrease afterward; by choosing different types of defects, the magnetic moments can be tuned over a broad range, for example, from 3 to 6 μB for GNCr. The intriguing element‐ and defect‐dependent magnetic behavior is further understood from electron‐ and back‐donation mechanisms.