Fibronectin conformation switch induced by coadsorption with human serum albumin

The dynamic adsorption of human serum albumin (HSA) and plasma fibronectin (Fn) onto hydrophobic poly(hydroxymethylsiloxane) (PHMS) and the structures of adsorbed protein layers from single and binary protein solutions were studied. Spectroscopic ellipsometry (SE) and quartz crystal microbalance with dissipation monitoring (QCM-D) together with atomic force microscopy (AFM) were used to measure the effective mass, thickness, viscoelastic properties, and morphology of the adsorbed protein films. Adsorbed HSA formed a rigid, tightly bound monolayer of deformed protein, and Fn adsorption yielded a thick, very viscoelastic layer that was firmly bound to the substrate. The mixed protein layers obtained from the coadsorption of binary equimolecular HSA-Fn solutions were found to be almost exclusively dominated by Fn molecules. Further sequential adsorption experiments showed little evidence of HSA adsorbed onto the predeposited Fn layer (denoted as Fn ? HSA), and Fn was not adsorbed onto predeposited HSA (HSA ? Fn). The conformational arrangement of the adsorbed Fn was analyzed in terms of the relative availability of two Fn domains. In particular, (4)F(1)·(5)F(1) binding domains in the Hep I fragment, close to the amino terminal of Fn, were targeted using a polyclonal antifibronectin antibody (anti-Fn), and the RGD sequence in the 10th segment, in the central region of the molecule, was tested by cell culture experiments. The results suggested that coadsorption with HSA induced the Fn switch from an open conformation, with the amino terminal subunit oriented toward the solution, to a close conformation, with the Fn central region oriented toward the solution.     

Design,synthesis and molecular docking of new [1,2,4] triazolo[4,3-a]quinoxaline derivatives as anticancer agents targeting VEGFR-2 kinase

Molecular Diversity - Vascular endothelial growth factor receptor-2 (VEGFR-2) is critically involved in cancer angiogenesis. Blocking of VEGFR-2 signaling pathway proved effective suppression of...     

Separation and quantitation of oxprenolol in urine and pharmaceutical formulations by HPLC using a Chiralpak IC and UV detection

Abstract  

A stereoselective HPLC method has been developed for the simultaneous determination of oxprenolol enantiomers in urine and pharmaceutical products. Enantiomeric resolution of oxprenolol was achieved on cellulose tris(3,5-dichlorophenylcarbamate) immobilized onto a 5 μm spherical porous silica chiral stationary phase (CSP) known as Chiralpak IC with UV detection at 273 nm. The mobile phase consisted of n-hexane:isopropanol:triethylamine 70:30:0.1 (v/v/v) at a flow rate of 1.0 cm³/min. The method was validated for its linearity, accuracy, precision, and robustness. The calibration curves were linear over the range of 0.5–75 μg/cm³, with a detection limit of 0.1 μg/cm³ for each enantiomer. An average recovery of 99.0% and a mean relative standard deviation of 2.6% at 40.0 μg/cm³ for S-(−)- and R-(+)-enantiomers were obtained. The overall recoveries of oxprenolol enantiomers from pharmaceutical formulations were in the range 97.5–99.0%, with RSDs ranging from 0.6 to 0.8%. The mean extraction efficiency of oxprenolol from urine was in the range of 86.0–93.0% at 0.5–5 μg/cm³ for each enantiomer. The assay method proved to be suitable as a chiral quality control for oxprenolol formulations using HPLC and for therapeutic drug monitoring.     

Highly sensitive methanol chemical sensor based on undoped silver oxide nanoparticles prepared by a solution method

We have prepared silver oxide nanoparticles (NPs) by a simple solution method using reducing agents in alkaline medium. The resulting NPs were characterized by UV–vis and FT-IR spectroscopy, X-ray powder diffraction, and field-emission scanning electron microscopy. They were deposited on a glassy carbon electrode to give a sensor with a fast response towards methanol in liquid phase. The sensor also displays good sensitivity and long-term stability, and enhanced electrochemical response. The calibration plot is linear (r ²?=?0.8294) over the 0.12?mM to 0.12?M methanol concentration range. The sensitivity is ~2.65?μAcm^?2?mM^?1, and the detection limit is 36.0?μM (at a SNR of 3). We also discuss possible future prospective uses of this metal oxide semiconductor nanomaterial in terms of chemical sensing.

Synthesis, molecular docking and preliminary in-vitro cytotoxic evaluation of some substituted tetrahydro-naphthalene (2',3',4',6'-tetra-O-acetyl-β-D-gluco/-galactopyranosyl) derivatives

A facile, convenient and high yielding synthesis of novel S-glycosides and N-glycosides incorporating 1,2,3,4-tetrahydronaphthalene and or 1,2-dihydropyridines moieties has been described. The aglycons 2, 4, and 7 were coupled with different activated halosugars in the presence of basic and acidic medium. The preliminary in-vitro cytotoxic evaluation revealed that compounds 3c, 3f, 5c and 7b show promising activity. A molecular docking study was performed against tyrosine kinase (TK) (PDB code: 1t46) by Autodock Vina. The docking output was analyzed and some compounds have shown hydrogen bond (H-B) formation with reasonable distances ranged from 2.06 A° to 3.06 A° with Thr 670 and Cys 673 residues found in the specified pocket. No hydrogen bond was observed with either Glu 640 nor Asp 810 residues, as was expected from pdbsum.     

Prediction of some quality attributes of lamb meat using near-infrared hyperspectral imaging and multivariate analysis

The goal of this study was to explore the potential of near-infrared (NIR) hyperspectral imaging in combination with multivariate analysis for the prediction of some quality attributes of lamb meat. In this study, samples from three different muscles (semitendinosus (ST), semimembranosus (SM), longissimus dorsi (LD)) originated from Texel, Suffolk, Scottish Blackface and Charollais breeds were collected and used for image acquisition and quality measurements. Hyperspectral images were acquired using a pushbroom NIR hyperspectral imaging system in the spectral range of 900–1700 nm. A partial least-squares (PLS) regression, as a multivariate calibration method, was used to correlate the NIR reflectance spectra with quality values of the tested muscles. The models performed well for predicting pH, colour and drip loss with the coefficient of determination (R²) of 0.65, 0.91 and 0.77, respectively. Image processing algorithm was also developed to transfer the predictive model in every pixel to generate prediction maps that visualize the spatial distribution of quality parameter in the imaged lamb samples. In addition, textural analysis based on gray level co-occurrence matrix (GLCM) was also conducted to determine the correlation between textural features and drip loss. The results clearly indicated that NIR hyperspectral imaging technique has the potential as a fast and non-invasive method for predicting quality attributes of lamb meat.     

Miniaturization through lab-on-a-chip: Utopia or reality for routine laboratories? A review

Micro total analysis (μTAS), also called “lab-on-a-chip (LOC)” technology, promises solutions for high throughput and highly specific analysis for chemistry, biology and medicine, while consuming only tiny amounts of samples, reactants and space. This article reports selected contributions of LOC, which represent clear practical approaches for routine work, or presenting potentiality to be transferred to routine analytical laboratories. Taking into account the present LOC state-of-the-art, we identify various reasons for its scarce implementation in routine analytical laboratories despite its high analytical potential, as well as the probably main “niche” for successfully practical developments is suggested.     

Cytotoxic gold compounds: synthesis, biological characterization and investigation of their inhibition properties of the zinc finger protein PARP-1

The new gold(III) complexes: [Au{2-(2'-pyridyl)imidazolate}Cl(2)] and [Au{2,6-bis(2'-benzimidazolate)pyridine}(OCOCH(3))] and the mono- and binuclear gold(I) complexes: [Au{2-(2'-pyridyl)imidazole}(PPh(3))](PF(6)), [Au(2-phenylimidazolate)(DAPTA)] (DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane), [(PPh(3)Au)(2)(2-R-imidazolate)](PF(6)) (R = 2-C(5)H(4)N, Ph) have been synthesized and characterized. The structure of the [(PPh(3)Au)(2){2-(2'-pyridyl)imidazolate)](PF(6)) complex was also characterized by X-ray crystallography. The antiproliferative properties of the complexes were assayed against human ovarian carcinoma cell lines, either sensitive (A2780) or resistant to cisplatin (A2780cisR), human mammary carcinoma cells (MCF7) and non-tumorigenic human kidney (HEK293) cells. Most of the studied compounds showed important cytotoxic effects. Interestingly, the compounds containing the 2-(2'-pyridyl)imidazolate ligand showed selectivity towards cancer cells with respect to the non-tumorigenic ones, with the dinuclear compound [(PPh(3)Au)(2){2-(2'-pyridyl)imidazolate)](PF(6)) being the most active. Some compounds were also screened for their inhibitory effect of the zinc-finger protein PARP-1, essential for DNA repair and relevant to the mechanisms of cancer cell resistance to cisplatin. Interaction studies of the compounds with the model protein ubiquitin were undertaken by electrospray ionization mass spectrometry (ESI MS). The results are discussed in relation to the putative mechanisms of action of the cytotoxic gold compounds.