Structural biology of the thioester-dependent degradation and synthesis of fatty acids

The fatty acid degradation and synthesis pathways consist of the same four chemical transformations. These transformations are facilitated by conjugating the fatty acid, via a thioester bond, to coenzyme A or acyl carrier protein in, respectively, the degradation and synthesis pathways. These pathways are compartmentalized in the peroxisomes, mitochondria and cytosol of eukaryotic cells. Current structural knowledge of the enzymes comprising these pathways shows that the approximately 130 entries in the RCSB Protein Data Bank can be grouped into seven superfamilies. Multifunctional enzymes are important in both pathways.     

A QSAR study on some series of anti-hepatitis B virus (HBV) agents

A quantitative structure-activity relationship (QSAR) study has been made on some series of anti-hepatitis B virus (HBV) agents, namely, a series of novel bis(L-amino acid) ester prodrugs of 9-[2--(phosphonomethoxy)ethyl]adenine, a similar series of compounds comprising of 2- amino-6-arylthio-9-[2-(phosphonoethoxy)ethyl] purine bis(2,2,2- trifluoroethyl) esters, and a series of 1-isopropylsulfonyl-2-amine benzimidazoles. In each case significant correlations are found between the anti-HBV potencies and some physicochemical and steric properties of the compounds, indicating that for the first two series the activity is controlled by the hydrophobic and the bulk properties of the molecules and, for the third series, the steric and hydrogen bonding properties of compounds are crucial for their anti-HBV potency.     

Genetic differentiation and diversity analysis of medicinal tree Syzygium cumini (Myrtaceae) from ecologically different regions of India

This study represents the agro-ecological zone wise surveys of molecular variation of important medicinal tree Syzygium cumini Linn. (Jamun) which is native to India. It is used world wide in treatment of diabetes. Despite of its diverse medicinal properties no molecular data is available about the pattern of variation in its natural range. Populations of S. cumini in India are located in different habitats which differ from each other with regard to ecological factors. In this study, random amplified polymorphic DNA (RAPD) markers were used to detect inter and intra levels of genetic variations of sixteen S. cumini genotypes collected from three major agro-ecological zones of India. A total of 220 amplification products were scored of which 87.50 % were polymorphic. The level of polymorphism ranged from 47.69 % to 74.87 % polymorphic bands per population and was correlated with population size. Different measures of diversity: Shannon’s index of phenotypic diversity (I) = 0.451 ± 0.230; Nei’s genetic diversity (h) = 0.300 ± 0.172; effective number of alleles per locus (Ne) = 1.51 ± 0.347; total species diversity (Hsp) = 0.315 ± 0.031 and within population diversity (Hpop) = 0.158 ± 0.104 showed high genetic diversity at species level. Coefficient of genetic differentiation (Gst =0.498; Nm = 0.503) revealed significant genetic differentiation among the populations. Most of the genetic variations are contained among the populations. The results of cluster analysis and principal component analysis (PCA) give only little evidence for an ecotypic differentiation of S. cumini populations. Present genetic structure of population suggests ex situ conservation in seed banks in which seeds from at least five populations need to collected and conserved. Secondly, our study provides practical information to herbal drugs manufactures who use Jamun as a raw material.     

Salivary gland branching morphogenesis

Salivary gland branching morphogenesis involves coordinated cell growth, proliferation, differentiation, migration, apoptosis, and interaction of epithelial, mesenchymal, endothelial, and neuronal cells. The ex vivo analysis of embryonic mouse submandibular glands, which branch so reproducibly and beautifully in culture, is a powerful tool to investigate the molecular mechanisms regulating epithelium-mesenchyme interactions during development. The more recent analysis of genetically modified mice provides insight into the genetic regulation of branching morphogenesis. The review begins, as did the field historically, focusing on the role of the extracellular matrix (ECM), and its components such as glycosaminoglycans, collagens, and laminins. Following sections describe the modification of the ECM by proteases and the role of cell-matrix and cell-cell receptors. The review then focuses on two major families of growth factors implicated in salivary gland development, the fibroblast growth factors (FGFs) and the epidermal growth factors (EGFs). The salivary gland phenotypes in mice with genetic modification of FGFs and their receptors highlight the central role of FGFs during salivary gland branching morphogenesis. A broader section mentions other molecules implicated from analysis of the phenotypes of genetically modified mice or organ culture experiments. The review concludes with speculation on some future areas of research.     

Simultaneous determination of metoprolol succinate and amlodipine besylate in human plasma by liquid chromatography-tandem mass spectrometry method and its application in bioequivalence study

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of metoprolol succinate (MPS) and amlodipine besylate (AM) using hydrochlorothiazide (HCTZ) as IS in human plasma. Both the drugs were extracted by simple liquid-liquid extraction with chloroform. The chromatographic separation was performed on a reversed-phase peerless basic C18 column with a mobile phase of methanol-water containing 0.5% formic acid (8:2, v/v). The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The method was validated over the concentration range of 1-100ng/ml for MPS and 1-15ng/ml AM in human plasma. The MRM transition of m/z 268.10-103.10, m/z 409.10-334.20 and m/z 296.00-205.10 were used to measure MPS, AM and HCTZ (IS), respectively. This method was successfully applied to the pharmacokinetic study of fixed dose combination (FDC) of MPS and AM formulation product after an oral administration to Indian healthy human volunteers.