Toward the identification of a reliable 3D QSAR pharmacophore model for the CCK2 receptor antagonism

The present study describes application of computational approaches to identify a validated and reliable 3D QSAR pharmacophore model for the CCK-2R antagonism through integrated ligand and structure based studies using anthranilic sulfonamide and 1,3,4-benzotriazepine based CCK-2R antagonists. The best hypothesis consisted five features viz. two aliphatic hydrophobic, one aromatic hydrophobic, one H-bond acceptor, and one ring aromatic feature with an excellent correlation for 34 training set (r2(training) = 0.83) and 58 test set compounds (r2(test) = 0.74). This model was validated through F-test and docking studies at the active site of the plausible CCK-2R where the 99% significance and well corroboration with the pharmacophore model respectively describes the model's reliability. The model also predicts well to other known clinically effective CCK-2R antagonists. Therefore, the developed model may useful in finding new scaffolds that may aid in design and develop new chemical entities (NCEs) as potent CCK-2R antagonists before their synthesis.     

Anticancer β-hairpin peptides: membrane-induced folding triggers activity

Several cationic antimicrobial peptides (AMPs) have recently been shown to display anticancer activity via a mechanism that usually entails the disruption of cancer cell membranes. In this work, we designed an 18-residue anticancer peptide, SVS-1, whose mechanism of action is designed to take advantage of the aberrant lipid composition presented on the outer leaflet of cancer cell membranes, which makes the surface of these cells electronegative relative to the surface of noncancerous cells. SVS-1 is designed to remain unfolded and inactive in aqueous solution but to preferentially fold at the surface of cancer cells, adopting an amphiphilic β-hairpin structure capable of membrane disruption. Membrane-induced folding is driven by electrostatic interaction between the peptide and the negatively charged membrane surface of cancer cells. SVS-1 is active against a variety of cancer cell lines such as A549 (lung carcinoma), KB (epidermal carcinoma), MCF-7 (breast carcinoma), and MDA-MB-436 (breast carcinoma). However, the cytotoxicity toward noncancerous cells having typical membrane compositions, such as HUVEC and erythrocytes, is low. CD spectroscopy, appropriately designed peptide controls, cell-based studies, liposome leakage assays, and electron microscopy support the intended mechanism of action, which leads to preferential killing of cancerous cells.     

Synergic effect of multi-walled carbon nanotubes and gold nanoparticles towards immunosensing of ricin with carbon nanotube-gold nanoparticles-chitosan modified screen printed electrode

An amperometric immunosensor for the specific detection of Ricinus communis is reported. Screen printed electrodes (SPEs) were modified with gold nanoparticles (GNPs) loaded multiwalled carbon nanotubes (MWCNTs)-chitosan (Ch) film. The ratio of MWCNT and GNP was optimised to get best electrochemically active electrode. Sandwich immunoassay format was used for the immunosensing of ricin. The revealing antibodies tagged with the enzyme alkaline phosphatase (ALP) converts the substrate 1-naphthyl phosphate into 1-naphthol that was determined with the amperometric technique. The amperometric current obtained was correlated with the concentration of ricin. The prepared GNP-MWCNT-Ch-SPE showed high stability due to the Ch film, short response time with good reproducibility and increased shelf life of the electrodes immobilised with antibodies. The electrochemical activity of the electrode improved because of optimization of composition of CNTs and gold nanoparticles. Under the optimal conditions, the modified electrode showed a wide linear response to the concentration of ricin in the range of 2.5-25 ng mL(-1) with a limit of detection of 2.1 ng mL(-1) and with a relative standard deviation of 5.1% and storage life of 32 days.     

"Turn on" electron-transfer-based selective detection of ascorbic acid via copper complexes immobilized on glass

"Turn-on" optical detection of parts-per-million (ppm) levels of ascorbic acid (AA) in water has been determined using a redox-active monolayer on glass.     

Monodisperse Co,Zn-Ferrite nanocrystals: Controlled synthesis,characterization and magnetic properties

Co_xZn_yFe_3−x−yO₄ ferrite (x=1 to 0; y=0 to1) nanocrystals have been synthesized by reverse microemulsion method. The nanocrystals are then comprehensively characterized by X-ray diffraction, Fourier transform infrared spectroscopy, Field emission transmission electron microscopy (FETEM), and magnetic properties were measured by using Vibrating sample magnetometer. X-ray analysis showed that all the crystals were cubic spinel. The lattice constant increased with the increase in Zn substitution. FETEM reveals that particle size varies in the range from 3 to 6 nm. As the concentration of Zn increases the magnetic behavior varies from ferromagnetic at y=0 and 0.2 to superparamagnetic to paramagnetic at y=1. The Curie temperature decreases with increasing concentration of Zn.     

Magnetoresistance studies of MeV ranged H and C ion irradiated HOPG flakes

2 MeV protons and 1 MeV carbon ions are bombarded on highly oriented pyrolytic graphite (HOPG) samples and their electronic transport measurements are carried out in the presence of magnetic field. The Magneto-Resistance (MR) measurements show measurable hysteresis in the resistance value after ion beam irradiation for the in-plane magnetic field direction as well as for the out-of-plane field direction. The MR depends on the thickness of the flake and the method of its separation from the bulk HOPG. The results substantiate that the ferromagnetic coupling between the magnetic moments at the vacancy defect sites in HOPG sensitively depends on the average defect separation. The average defect separation range of 1.7–0.5 nm allows only a part of the 40 μm thick proton beam irradiated sample to go for ferromagnetic ordering. Similar conclusions are drawn from carbon ion irradiated HOPG flake. The irradiation increases the resistance of the flake as well.     

Range‐independent background subtraction algorithm for recovery of Raman spectra of biological tissue

An important requirement for the use of Raman spectroscopy for tissue diagnostic applications is an appropriate algorithm that can faithfully retrieve weak tissue Raman signals from the measured raw Raman spectra. Although iterative modified polynomial‐fitting‐based automated algorithms are widely used, these are sensitive to the choice of the fitting range, thereby leading to significantly different Raman spectra for different start and stop wavenumber selection. We report here an algorithm for automated recovery of the weak Raman signal, which is range independent. Given a raw Raman spectrum and the choice of the start and the stop wavenumbers, the algorithm first truncates the spectrum to include the raw data within this wavenumber range, linearly extrapolates the truncated raw spectrum beyond the points of truncation on the two sides by using coefficients of linear least‐square fit, adds two Gaussian peaks of appropriate height and width on the extrapolated linear wings on either side and then iteratively smoothens the data with all these add‐ons such that the smaller of the ordinate values of the smoothed and the starting raw data serve as the input to each successive round of iterative smoothing until the added Gaussian peaks are fully recovered. The algorithm was compared with the modified polynomial‐based algorithms using mathematically simulated Raman spectrum as well as experimentally measured Raman spectra from various biological samples and was found to yield consistently range‐independent and artifact‐free Raman signal with zero baseline. Copyright © 2012 John Wiley & Sons, Ltd.     

A lattice dynamical investigation for the Raman and the infrared frequencies of Bi2W2O9

Studies on infrared and Raman-active phonons in the Aurivillius ferroelectric Bi₂W₂O₉ were performed theoretically. The Raman and infrared phonons were calculated by applying a short-range force constant model using normal coordinates having space group Pna2₁. Sixteen stretching, two repulsive and seventeen bending force constants were used for the calculations of the zone center phonons. The calculated Raman and infrared wavenumbers are in very good agreement with the experimental ones in the literature. Potential energy distribution for this compound has also been investigated for the contribution of each force constant towards the Raman and the infrared wavenumbers.