Sialidase inhibitors related to zanamivir: synthesis and biological evaluation of 4H-pyran 6-ether and ketone.

Synthesis of 5R-Acetamido-4S-amino-4H-pyran-6R-O-( -ethyl)propyl and 6R-(1-oxo-2-ethyl)butyl 2-carboxylic acids (4 and 5) and their evaluation as inhibitors of influenza virus sialidase is described. Both compounds showed good inhibitory activity with marked selectivity for influenza A sialidase.

A novel clan of zinc metallopeptidases with possible intramembrane cleavage properties.

Computer-based database searching and protein multiple sequence alignment has identified a novel clan of zinc metallopeptidases, which, by phylogenetic analysis, has been shown to contain six subfamilies. The family is characterized by four common transmembrane segments and three conserved sequence motifs. The combination of topology analysis and motif identification has detected three potential Zn2+ coordinating residues.

JavaShade: multiple sequence alignment box-and-shading on the World Wide Web.

Results: JavaShade is a multiple sequence alignment box-and-shade tool for generating high quality printed output that uses a variety of methods for boxing and shading, allowing the most appropriate functions to be chosen for displaying the most meaningful positions in an alignment.

Availability: JavaShade is available from the WWW at http://industry.ebi.

Cloning and characterization of alternative mRNA forms for the rat metabotropic glutamate receptors mGluR7 and mGluR8.

Novel mRNA isoforms for two members of the group III metabotropic glutamate receptors (mGluRs), called mGluR7b and mGluR8b, were identified from rat brain cerebral cortex and hippocampus. In both cases, the alternative splicing is generated by a similar out-of-frame insertion in the carboxyl-terminus that results in the replacement of the last 16 amino acids of mGluR7 and mGluR8 by 23 and 16 different amino acids, respectively. Distribution analysis for mGluR7 and mGluR8 isoforms revealed that the two splice variants are generally coexpressed in the same brain areas.

Immunohistochemical localization of the mGluR1beta metabotropic glutamate receptor in the adult rodent forebrain: evidence for a differential distribution of mGluR1 splice variants.

Alternative splicing has been shown to occur at the metabotropic glutamate receptor 1 (mGluR1) gene. Three main isoforms that differ in their carboxy-termini have been described so far and named mGluR1alpha, mGluR1beta and mGluR1c. These variants when expressed in recombinant systems all activate phospholipase C, although the [Ca2+] signals generated have different kinetics.

Characterization of perforant path lesions in rodent models of memory and attention.

Early stage Alzheimer's disease (AD) pathology is associated with neurodegeneration of systems within the temporal cortex, e.g. the entorhinal cortex, perforant pathway and hippocampus.

Characterisation of impurities in bulk drug batches of fluticasone propionate using directly coupled HPLC-NMR spectroscopy and HPLC-MS.

Directly coupled HPLC NMR spectroscopic and HPLC-MS approaches have been used to confirm the identity of four known dimeric impurities in a partially purified batch of fluticasone propionate each at levels of 0.06-0.9% of parent compound based on UV absorption.

Lewis X biosynthesis in Helicobacter pylori. Molecular cloning of an alpha(1,3)-fucosyltransferase gene.

The lipopolysaccharide of certain strains of Helicobacter pylori was recently shown to contain the Lewis X (Lex) trisaccharide (Galbeta-1, 4-(Fucalpha(1,3))-GlcNAc). Lex is an oncofetal antigen which appears on human gastric epithelium, and its mimicry by carbohydrate structures on the surface of H. pylori may play an important part in the interaction of this pathogen with its host.

Potentiation of NMDA and AMPA responses by group I mGluR in spinal cord motoneurons.

Application of the metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and the Group I selective mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) potentiated NMDA- and AMPA-induced potential changes recorded from ventral roots of the isolated hemisected baby rat spinal cord. Potentiation produced by 1S,3R-ACPD was completely abolished by the Group I selective mGluR antagonists (S)-4-carboxyphenylglycine (4CPG) or (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). In addition, the protein kinase C (PKC) blockers staurosporine or chelerythrine chloride were able to antagonize the 1S,3R-ACPD-induced potentiation of both NMDA and AMPA response, suggesting that the enhancing effect induced by Group I mGluRs is modulated by a PKC-mediated mechanism.

Chromatographic Hydrophobicity Index by Fast-Gradient RP-HPLC: A High-Throughput Alternative to log P/log D.

A new chromatographic hydrophobicity index (CHI) is described which can be used as part of a protocol for high-throughput (50-100 compounds/day) physicochemical property profiling for rational drug design. The index is derived from retention times (t(R)) observed in a fast gradient reversed-phase HPLC method. The isocratic retention factors (log k') were measured for a series of 76 structurally unrelated compounds by using various concentrations of acetonitrile in the mobile phase.

Delineation of the arginine- and tetrahydrobiopterin-binding sites of neuronal nitric oxide synthase.

Nitric oxide synthase (EC 1.14.13.

The role of ranitidine bismuth citrate in significantly reducing the emergence of Helicobacter pylori strains resistant to antibiotics.

Background: This study was carried out to investigate the clinical observation that the emergence of antibiotic resistance can be reduced in Helicobacter pylori if agents are administered in combination with bismuth salts.

Materials And Methods: Two H. pylori clinical isolates were grown on chocolate Columbia agar containing either ranitidine bismuth citrate (RBC) at one-half lethal concentration (8 micrograms/ml) or no drug control for 22 subcultures.