bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide Structure Stabilization by Membrane Anchoring and its General Applicability to the Development of Potent Cell‐Permeable Inhibitors
Authors: Johannessen Liv , Remsberg Jarrett , Gaponenko Vadim , Adams Kristie M. , Barchi Joseph J. , Tarasov Sergey G. , Jiang Sheng , Tarasova Nadya I. 
Published: March 2011

AbstractIsolated protein motifs that are involved in interactions with their binding partners can be used to inhibit these interactions. However, peptides corresponding to protein fragments tend to have no defined secondary or tertiary structure in the absence of scaffolding by the rest of protein molecule. This results in low inhibitor potency. NMR and CD spectroscopy studies of lipopeptide inhibitors of the Hedgehog pathway revealed that membrane anchoring allows the cell membrane to function as a scaffold and facilitate the folding of short peptides. In addition, lipidation enhances cell permeability and increases the concentration of the compounds near the membrane, thus facilitating potent inhibition. The general applicability of this rational approach was further confirmed by the generation of selective antagonists of the insulin‐like growth factor 1 receptor with GI50 values in the nanomolar range. Lipopeptides corresponding to protein fragments were found to serve as potent and selective inhibitors of a number of nondruggable molecular targets.
Influence of Substrate Dideuteration on the Reaction of the Bifunctional Heme Enzyme Psi Factor Producing Oxygenase A (PpoA)
Authors: Nadler André , Koch Christian , Brodhun Florian , Wehland Jan‐Dirk , Tittmann Kai , Feussner Ivo , Diederichsen Ulf 
Published: March 2011

AbstractPpoA is a bifunctional enzyme that catalyzes the dioxygenation of unsaturated C18 fatty acids. The products of this reaction are termed psi factors and have been shown to play a crucial role in conferring a balance between sexual and asexual spore development as well as production of secondary metabolites in the fungus Aspergillus nidulans. Studies on the reaction mechanism revealed that PpoA uses two different heme domains to catalyze two subsequent reactions. Initially, the fatty acid substrate is dioxygenated at C8, yielding an 8‐hydroperoxy fatty acid at the N‐terminal domain. This reaction is catalyzed by a peroxidase/dioxygenase‐type domain that exhibits many similarities to prostaglandin H2 synthases and involves a stereospecific homolytic hydrogen abstraction from C8 of the substrate. The C terminus harbors a heme thiolate P450 domain in which rearrangement of the 8‐hydroperoxide to the final product, a 5,8‐dihydroxy fatty acid, takes place. To obtain further information about the intrinsic kinetics and reaction mechanism of PpoA, we synthesized C5‐dideutero‐ and C8‐dideutero‐oleic acid by a novel protocol that offers a straightforward synthesis without employing the toxic additive hexamethylphosphoramide (HMPA) during CC coupling reactions or mercury salts upon thioketal deprotection. These deuterated fatty acids were then employed for kinetic analysis under multiple‐turnover conditions. The results indicate that the hydrogen abstraction at C8 is the rate‐determining step of the overall reaction because we observed a KIE (VH/VD) of ∼33 at substrate saturation that suggests extensive nuclear tunneling contributions for hydrogen transfer. Deuteration of the substrate at C5, however, had little effect on VH/VD but resulted in a different product pattern presumably due to an altered lifetime and partitioning of a reaction intermediate.
Design, Synthesis and Characterization of a New Anionic Cell‐Penetrating Peptide: SAP(E)
Authors: Martín Irene , Teixidó Meritxell , Giralt Ernest 
Published: March 2011

AbstractCell‐penetrating peptides (CPPs) are powerful tools to transport cell‐impermeable cargoes into the cytoplasm without damaging the cell membrane. The vast majority of these peptides described to date share several features, among others, they are positively charged at physiological pH. In several cases a clear correlation between an increasing number of positive charges and internalization properties has been reported. Here, we describe what, to the best of our knowledge, is the first anionic CPP. This new compound SAP(E) internalizes into a range of cell lines with good efficiency and it shows low toxicity. We also report on the internalization mechanism. The discovery of this new class of CPP opens the way to the intracellular delivery of new molecular cargoes.
Potent and Selective Synthetic Modulators of a Quorum Sensing Repressor in Pseudomonas aeruginosa Identified from Second‐Generation Libraries of N‐Acylated L‐Homoserine Lactones
Authors: Mattmann Margrith E. , Shipway Patrick M. , Heth Nicole J. , Blackwell Helen E. 
Published: March 2011

AbstractBacteria can coordinate group behavior using chemical signals in a process called quorum sensing (QS). The QS system in the opportunistic pathogen Pseudomonas aeruginosa is largely governed by the LasR receptor and its cognate chemical signal, N‐(3‐oxo)‐dodecanoyl L‐homoserine lactone (OdDHL). LasR also appears to share this signal with an orphan LuxR‐type receptor in P. aeruginosa, termed QscR, which represses LasR activity. Non‐native molecules that modulate QscR would represent valuable tools to study the role of this novel QS repressor protein in P. aeruginosa. We performed a critical analysis of previously identified, non‐native N‐acylated L‐homoserine lactone (AHL) activators and inhibitors of QscR to determine a set of structure–activity relationships (SARs). Based on these SAR data, we designed, synthesized, and screened several second‐generation libraries of AHLs for new ligands that could target QscR. These studies revealed the most active AHL agonists and antagonists of QscR reported to date, with activities ranging from nanomolar to low micromolar in a QscR bacterial reporter strain. Several of these AHLs were highly selective for QscR over LasR and other LuxR‐type receptors. A small subset of the new QscR activators, however, were also found to inhibit LasR; this demonstrates the exciting potential for the synergistic modulation of these integral P. aeruginosa QS receptors by using a single synthetic compound.
Water‐Soluble IrIII N‐Heterocyclic Carbene Based Catalysts for the Reduction of CO2 to Formate by Transfer Hydrogenation and the Deuteration of Aryl Amines in Water
Authors: Azua Arturo , Sanz Sergio , Peris Eduardo 
Published: March 2011

AbstractTwo new water‐soluble [IrI2(AcO)(bis‐NHC)] complexes (NHC=N‐heterocyclic carbene) incorporating a sulfonate functionality have been synthesized. The two complexes have been tested in the reduction of CO2 with H2 and iPrOH, and their activity has been compared with similar species without the sulfonate moiety. In both reactions, the complex with the two abnormally bound NHCs shows the best catalytic efficiencies, due to the higher σ‐electron‐donor character of the ligand. Remarkably, the activities obtained for the reduction of CO2 under the transfer hydrogenation conditions are the best reported to date in terms of TON value (max. TON=2700). The two new complexes have also shown very good activity in the selective deuteration of arylamines, a process that is known to proceed through a chelate assisted N‐directed process.
Comparison and validation of CFD models in liquid–solid suspensions
Authors: Visuri Olli , Liiri Maret , Alopaeus Ville 
Published: March 2011

AbstractA new simple method to validate CFD models in multiphase flows is presented. The experimental procedure used in this study is based on digital imaging and a simple algorithm to reduce the noise of an image. This method is inexpensive and easy to use and it can be applied to several liquid–solid systems where the liquid is transparent. The CFD modelling was done using a two‐fluid κ–ε model. Several drag correlations were tested in simulations with two impeller speeds and various particle sizes. The results were compared with experimental data. Comparison was also made with the just‐suspended speed correlation by Zwietering.
Explicit equations for laminar flow of herschel–bulkley fluids
Authors: Swamee Prabhata K. , Aggarwal Nitin 
Published: March 2011

AbstractThere are three typical problems encountered in pipe flows: unknown friction factor, unknown flow rate, and unknown diameter problems. A major problem in determining the solution to these flow problems occurs due to the implicit nature of the Darcy–Weisbach friction factor. Though explicit equations for flow of Newtonian fluids and Power Law fluids are available, no such usable equations exist for Herschel–Bulkley fluids. In this paper, explicit equations have been given for flow of Herschel–Bulkley fluids in the laminar regime.
A cell‐based screen for inhibitors of flagella‐driven motility in Chlamydomonas reveals a novel modulator of ciliary length and retrograde actin flow
Authors: Engel Benjamin D. , Ishikawa Hiroaki , Feldman Jessica L. , Wilson Christopher W. , Chuang Pao‐Tien , Snedecor June , Williams Janice , Sun Zhaoxia , Marshall Wallace F. 
Published: March 2011

AbstractCilia are motile and sensory organelles with critical roles in physiology. Ciliary defects can cause numerous human disease symptoms including polycystic kidneys, hydrocephalus, and retinal degeneration. Despite the importance of these organelles, their assembly and function is not fully understood. The unicellular green alga Chlamydomonas reinhardtii has many advantages as a model system for studies of ciliary assembly and function. Here we describe our initial efforts to build a chemical‐biology toolkit to augment the genetic tools available for studying cilia in this organism, with the goal of being able to reversibly perturb ciliary function on a rapid time‐scale compared to that available with traditional genetic methods. We screened a set of 5520 compounds from which we identified four candidate compounds with reproducible effects on flagella at nontoxic doses. Three of these compounds resulted in flagellar paralysis and one induced flagellar shortening in a reversible and dose‐dependent fashion, accompanied by a reduction in the speed of intraflagellar transport. This latter compound also reduced the length of cilia in mammalian cells, hence we named the compound “ciliabrevin” due to its ability to shorten cilia. This compound also robustly and reversibly inhibited microtubule movement and retrograde actin flow in Drosophila S2 cells. Ciliabrevin may prove especially useful for the study of retrograde actin flow at the leading edge of cells, as it slows the retrograde flow in a tunable dose‐dependent fashion until flow completely stops at high concentrations, and these effects are quickly reversed upon washout of the drug. © 2011 Wiley‐Liss, Inc.
Significant J‐shaped association between body mass index (BMI) and diabetic foot ulcers
Authors: Sohn Min‐Woong , Budiman‐Mak Elly , Lee Todd A. , Oh Elissa , Stuck Rodney M. 
Published: March 2011

AbstractBackgroundDisagreement exists regarding the relationship between body weight and foot ulceration risk among diabetic persons.MethodsWe used a nested case‐control design to estimate the association between body mass index (BMI) and 1‐year and 5‐year foot ulceration risk. We obtained data on all diabetic patients < 60 years of age who were treated in the US Department of Veterans Affairs healthcare system in 2003. Patient characteristics and co‐morbidities were obtained at baseline. For each individual with an incident foot ulcer (case), up to four individuals were randomly selected who matched the case on age, sex, race, marital status, and calendar time.ResultsCrude 1‐year and 5‐year incidence rates were 1.35 and 6.22% after a mean follow‐up of 11.8 ± 1.2 months and 55.5 ± 12.8 months, respectively. Compared with individuals with BMI 25–29.9 kg/m2, those with BMI 40–44.9 kg/m2 and those with BMI ≥ 45 kg/m2 had 25% [adjusted odds ratio (AOR) = 1.25; 95% confidence interval (CI), 1–1.56] and 83% (AOR = 1.83; 95% CI, 1.44–2.32) higher 1‐year risk and 1.4 (AOR = 1.39; 95% CI, 1.26–1.54) and 2.1 (AOR = 2.08; 95% CI, 1.86–2.32) times higher 5‐year risk. BMI < 25 kg/m2 was associated with 30% higher risk at both 1 year (AOR = 1.28; 95% CI, 1.04–1.58) and 5 years (AOR = 1.27; 95% CI, 1.15–1.40).ConclusionsOur data suggest a significant J‐shaped association between BMI and diabetic foot ulcers. Published 2011. This article is a US Government work and is in the public domain in the USA.
Rdh10 mutants deficient in limb field retinoic acid signaling exhibit normal limb patterning but display interdigital webbing
Authors: Cunningham Thomas J. , Chatzi Christina , Sandell Lisa L. , Trainor Paul A. , Duester Gregg 
Published: March 2011

AbstractRetinoic acid (RA) is purported to be required for expression of genes controlling proximodistal (Meis2) or anteroposterior (Shh) limb patterning. Embryos lacking RDH10, the primary enzyme synthesizing retinaldehyde during mouse development, survive until E14.5 with stunted forelimbs but apparently normal hindlimbs. Using embryos carrying the RARE‐lacZ RA‐reporter transgene, we show that endogenous RA activity in Rdh10trex/trex mutants is detected in neuroectoderm but not limbs during initiation and patterning. Treatment of Rdh10 mutants with 25 nM RA restores RARE‐lacZ activity to limb mesoderm, validating RARE‐lacZ and verifying that RA is absent in mutant limbs. In Rdh10 mutants, hindlimbs exhibit normal Meis2/Shh expression and skeletal patterning, and although forelimbs are growth‐retarded their Meis2 expression remains normal. Later in development, Rdh10 mutants lack interdigital RA activity and accordingly fail to exhibit normal loss of interdigital mesenchyme. These findings demonstrate that RA is unnecessary for limb patterning but required later for interdigital tissue loss. Developmental Dynamics 240:1142–1150, 2011. © 2011 Wiley‐Liss, Inc.
Keeping up with the zone of polarizing activity: New roles for an old signaling center
Authors: Harfe Brian D. 
Published: March 2011

AbstractThe vertebrate limb is an excellent model organ system to investigate how signaling pathways interact. Over the last half‐century, experiments investigating patterning in the vertebrate limb have led directly to the discovery of many of the molecules and molecular pathways that are not only responsible for limb patterning but the patterning of many different organ systems. In the limb bud, the zone of polarizing activity (ZPA) has long been known to produce factor(s) that are essential for normal limb formation. Recently, one of these factors, Sonic Hedgehog (SHH) was shown to function not only in the limb bud mesenchyme but also in the ectoderm overlying the ZPA. This review discusses the role and potential implications hedgehog signaling in the limb bud ectoderm plays in patterning the vertebrate limb. Developmental Dynamics 240:915–919, 2011. © 2011 Wiley‐Liss, Inc.
Synthesis and Characterization of Nickel(II) Aminoalkoxides: Application to Molecular Precursors for MOCVD of Ni Thin Films
Authors: Yoo Seung Ho , Choi Hana , Kim Hyo‐Suk , Park Bo Keun , Lee Sun Sook , An Ki‐Seok , Lee Young Kuk , Chung Taek‐Mo , Kim Chang Gyoun 
Published: March 2011

AbstractNovel single precursors for Ni, Ni(dmamp)2 (1), Ni(deamp)2 (2), and Ni(emamp)2 (3), were synthesized by the metathesis reaction between [Ni(NH3)6]Cl2 and two equiv. of Na(dmamp), Na(deamp), and Na(emamp), respectively. Complexes 1–3 have been characterized by IR, 1H NMR, and 13C NMR spectroscopies, and microanalytical data, as well as single‐crystal X‐ray diffraction studies. Through GC/MS analysis of the gaseous species generated by the decomposition of 1, a self‐reduction pathway to form metallic Ni was studied. By the metalorganic chemical vapor deposition of 1, metallic Ni hexagonal‐phase thin films were obtained at 250 °C and cubic‐phase thin films were obtained at 400 °C.
Synthesis and Theoretical Hirshfeld Analysis of a Supramolecular Heteropolyoxovanadate Architecture
Authors: Grabau Mathias , Forster Johannes , Heussner Kirsten , Streb Carsten 
Published: March 2011

AbstractA supramolecular heteropolyoxovanadate structure has been synthesized and characterized using single‐crystal XRD, powder XRD and a range of spectroscopic methods. The new compound, [tBuNH(C2H4OH)2]4[H5P1V14O42]·12H2O (1) was obtained using a one‐pot strategy starting from a simple inorganic vanadium oxide precursor and an amphiphilic cation in acidic aqueous solution. The cluster anion [H5P1V14O42]4– is based on the well‐known Keggin structure but in addition features two capping vanadyl [V=O]3+ units. In the crystal lattice, the clusters are arranged in linear 1D chains where neighbouring clusters are directly linked by one hydrogen bond. In addition, the assembly is stabilized by lattice water molecules and organic counterions which aggregate to form hydrophobic cavities with diameters of 0.6 nm. In order to analyze the supramolecular interactions leading to the cluster formation, we have used a combination of traditional structural analysis, theoretical bond valence sum (BVS) calculations and computational Hirshfeld surface analyses which allow the rapid determination of short‐ and long‐range intermolecular contacts. The applicability of the Hirshfeld analysis tool for complex ionic compounds is evaluated and the advantages as well as the limitations of the method are discussed. The combination of these techniques allowed us to assess the dominating intermolecular interactions and showed that the crystal packing is not only controlled by electrostatic interactions, but also by distinctive sets of hydrogen bonds and hydrophobic interactions between adjacent organic counterions.
Determination of Binding Constants of Hydrogen‐Bonded Complexes by ITC, NMR CIS, and NMR Diffusion Experiments
Authors: Dethlefs Christiane , Eckelmann Jens , Kobarg Hauke , Weyrich Thomas , Brammer Stefan , Näther Christian , Lüning Ulrich 
Published: March 2011

AbstractThe host–guest complex formation between barbital and various acylaminopyridyl isophthalamides (Hamilton receptors) has been determined quantitatively. The syntheses of nine isophthalamides are described. Their structures differ in the substitution patterns on the central isophthalic unit, and the natures of the acyl residues. Ethylhexanoyl derivatives proved to be more soluble than pentanoyl amides. The association constants were determined by 1H NMR titrations monitoring chemically induced shifts (CIS values), by 1H NMR diffusion experiments, and by isothermal titration calorimetry (ITC), giving Kass values in chloroform at 298 K between 33 × 103 and 100 × 103 M–1.
Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts: Enantioselective Propargylic Alkylation of Propargylic Alcohols Bearing an Internal Alkyne with Aldehydes
Authors: Motoyama Kazuki , Ikeda Masahiro , Miyake Yoshihiro , Nishibayashi Yoshiaki 
Published: March 2011

AbstractThe enantioselective propargylic alkylation of propargylic alcohols bearing an internal alkyne moiety with aldehydes in the presence of a metal salt as the Lewis acid and an optically active secondary amine as the co‐catalyst has been found to give the corresponding propargylic alkylated products in high yields as a mixture of two diastereoisomers with high enantioselectivity.
A basic phenylalanine‐rich oligo‐peptide causes antibody cross‐reactivity
Authors: Luo Gangyue , Quan Guanghua , Guo Jinya , Zhang Haijiang , Li Sun , Wu Weidong , Nie Ling , Dong Yuliang , Wu Suhong , Zheng Guangni , Yang Jing , Xu Jie , Wang Weina 
Published: March 2011

AbstractGlycolate oxidase (GO) and ribulose‐1,5‐bisphosphate carboxylase/oxygenase (RubisCO) are the two enzymes that serve key functions in the photorespiration and photosynthesis of plants. A 2 kDa highly basic phenylalanine‐rich oligo‐peptide (BOP) binds to the surface of acidic GO via ionic and hydrophobic interactions, forming the GO‐BOP complex (GC). Previously, RubisCO was thought to exist as a single species composed of a large (rbc L, 54 kDa) and a small subunit (rbc S, 14 kDa). Here we show for the first time, using 2‐DE, SDS‐PAGE, immunoassays and amino acid determination, that BOP also interacts with RubisCO and that many RubisCO‐BOP complexes (RCs), differing in pI, hydrophobicity and activity, coexist in green leaves. GCs, RCs and crude extract from green leaves analyzed by SDS‐PAGE Western blotting showed that BOP exists either in subunit‐BOP complexes (GO subunit‐BOP, rbc L‐BOP and rbc S‐BOP etc.), with a wide variation in the number and the position of BOPs bound to each subunit molecular, or alone without a binding partner. When rbc L‐BOP and rbc S‐BOP were assayed by SDS‐PAGE, BOP was dissociated from the subunit and it self‐assembled to form 37 different BOP polymers (basic phenylalanine‐rich protein) whose molecular weights (Mrs) ranged from 34.0 to 91.6 kDa, indicating that the Mr of BOP is about 2 kDa. Thus, the addition of BOP changes the Mr of the subunit‐BOP complexes so minimally that the rbc L and rbc S run at their predicted Mrs on SDS‐PAGE. In summary, the results described here demonstrate that the presence of BOP in complexes (both subunit‐BOP complex and protein‐BOP complex) can cause cross‐reactivity of antibodies against different proteins.
A novel capillary electrophoretic method for determining aliphatic aldehydes in food samples using 2‐thiobarbituric acid derivatization
Authors: Zhang Jun‐Bo , Li Meng‐Jie , Li Wen‐Li , Chu Qing‐Cui , Ye Jian‐Nong 
Published: March 2011

AbstractA novel electrophoretic method for sensitive determination of nine aldehydes, including formaldehyde (C1), acetaldehyde (C2), propanal (C3), butanal (C4), pentanal (C5), hexanal (C6), glutaradehyde (Gla), 2,3‐butanedione (Bud) and methylgloxal (MGo) in food samples, has been developed based on CE with amperometric detection (CE‐AD). After being derivatized with an electroactive compound, 2‐thiobarbituric acid (TBA), these nine non‐electroactive aldehydes were converted to electroactive adducts, and therefore detectable by CE‐AD approach. Experimental conditions of derivatization and CE‐AD detection were optimized. The proposed method was validated according to International Conference on Harmonization (ICH) requirements, with recovery results ranging from 82.8 to 123.8%. Calibration plots of aliphatic aldehydes were linear (r2≥0.9901) in the concentration range from 0.083 to 15.0 mg/L. The LODs were between 0.008 and 0.074 mg/L. The proposed CE‐AD method provides a reliable and sensitive quantitative evaluation for non‐electroactive low‐molecular‐mass monoaldehydes and dialdehydes in real sample matrices by employing relatively simple and inexpensive instrument.
Rapid analysis of phosphoamino acids from phosvitin by near‐infrared cyanine 1‐(ε‐succinimydyl‐hexanoate)‐1′‐methyl‐3,3,3′,3′‐tetramethyl‐indocarbocyanine‐5,5′‐disulfonate potassium derivatization and polyacrylamide‐coated CE with LIF detection
Authors: Fu Ni‐Na , Wang Hong , Zhang Hua‐Shan 
Published: March 2011

AbstractA polyacrylamide‐coated CE method with LIF detection was developed for analyzing three phosphoamino acids including phosphotyrosine (p‐Tyr), phosphothreonine (p‐Thr), and phosphoserine (p‐Ser). A near‐infrared dye, 1‐(ε‐succinimydyl‐hexanoate)‐1′‐methyl‐3,3,3′,3′‐tetramethyl‐indocarbocyanine‐5,5′‐disulfonate potassium (MeCy5‐OSu) was employed for derivatization of these phosphoamino acids. Results indicated that the complete baseline resolution of each phosphoamino acid was obtained within 6.1 min, using 10 mmol/L phosphate buffer (pH 4.0) containing 60 mmol/L SDS as running buffer. The highest derivatization efficiency was achieved in 0.2 mol/L borate buffer (pH 8.8) for 30 min at 30°C. Linearity of response was found in the range of 0.05–1 μmol/L. The correlation coefficients for these phosphoamino acids were from 0.9940 to 0.9976. The LODs for phosphotyrosine, phosphothreonine, and phosphoserine were about 6, 8, and 8 nmol/L, respectively. The proposed method has been successfully applied to the determination of phosphoamino acids in the hydrolysis sample of a phosphorylated phosvitin. Average recoveries for phosvitin sample were in the range of 94.0–98.0% and coefficients of variation ranged from 2.7 to 4.8%.