Copper-catalyzed asymmetric oxidation of sulfides

Copper-catalyzed asymmetric sulfoxidation of aryl benzyl and aryl alkyl sulfides, using aqueous hydrogen peroxide as the oxidant, has been investigated. A relationship between the steric effects of the sulfide substituents and the enantioselectivity of the oxidation has been observed, with up to 93% ee for 2-naphthylmethyl phenyl sulfoxide, in modest yield in this instance (up to 30%). The influence of variation of solvent and ligand structure was examined, and the optimized conditions were then used to oxidize a number of aryl alkyl and aryl benzyl sulfides, producing sulfoxides in excellent yields in most cases (up to 92%), and good enantiopurities in certain cases (up to 84% ee)

Asymmetric oxidation of sulfides

This review discusses synthesis of enantiopure sulfoxides through the asymmetric oxidation of prochiral sulfides. The use of metal complexes to promote asymmetric sulfoxidation is described in detail, with a particular emphasis on the synthesis of biologically active sulfoxides. The use of non-metal-based systems, such as oxaziridines, chiral hydroperoxides and peracids, as well as enzyme-catalyzed sulfoxidations is also examined

Synthesis of enantioenriched sulfoxides

This review discusses strategies for the asymmetric synthesis of sulfoxides, compounds with many applications in stereoselective synthesis and in some cases with pharmaceutical application. The review describes asymmetric oxidation, including metal catalyzed and non-metal and biological oxidation processes, in addition to synthetic approaches via nucleophilic substitution of appropriately substituted precursors. Kinetic resolution in oxidation of sulfoxides to the analogous sulfones is also discussed; in certain instances, access to enantioenriched sulfoxides can be achieved via a combination of asymmetric sulfide oxidation and complementary kinetic resolution in sulfoxide oxidation

Bacteriophages and bacterial plant diseases

Losses in crop yields due to disease need to be reduced in order to meet increasing global food demands associated with growth in the human population. There is a well-recognized need to develop new environmentally friendly control strategies to combat bacterial crop disease. Current control measures involving the use of traditional chemicals or antibiotics are losing their efficacy due to the natural development of bacterial resistance to these agents. In addition, there is an increasing awareness that their use is environmentally unfriendly. Bacteriophages, the viruses of bacteria, have received increased research interest in recent years as a realistic environmentally friendly means of controlling bacterial diseases. Their use presents a viable control measure for a number of destructive bacterial crop diseases, with some phage-based products already becoming available on the market. Phage biocontrol possesses advantages over chemical controls in that tailor-made phage cocktails can be adapted to target specific disease-causing bacteria. Unlike chemical control measures, phage mixtures can be easily adapted for bacterial resistance which may develop over time. In this review, we will examine the progress and challenges for phage-based disease biocontrol in food crops

Inhibition of the growth of Bacillus subtilis DSM10 by a newly discovered antibacterial protein from the soil metagenome

A functional metagenomics based approach exploiting the microbiota of suppressive soils from an organic field site has succeeded in the identification of a clone with the ability to inhibit the growth of Bacillus subtilis DSM10. Sequencing of the fosmid identified a putative β-lactamase-like gene abgT. Transposon mutagenesis of the abgT gene resulted in a loss in ability to inhibit the growth of B. subtilis DSM10. Further analysis of the deduced amino acid sequence of AbgT revealed moderate homology to esterases, suggesting that the protein may possess hydrolytic activity. Weak lipolytic activity was detected; however the clone did not appear to produce any β-lactamase activity. Phylogenetic analysis revealed the protein is a member of the family VIII group of lipase/esterases and clusters with a number of proteins of metagenomic origin. The abgT gene was sub-cloned into a protein expression vector and when introduced into the abgT transposon mutant clones restored the ability of the clones to inhibit the growth of B. subtilis DSM10, clearly indicating that the abgT gene is involved in the antibacterial activity. While the precise role of this protein has yet to fully elucidated, it may be involved in the generation of free fatty acid with antibacterial properties. Thus functional metagenomic approaches continue to provide a significant resource for the discovery of novel functional proteins and it is clear that hydrolytic enzymes, such as AbgT, may be a potential source for the development of future antimicrobial therapies

A click chemistry route to 2-functionalised PEGylated and cationic beta-cyclodextrins: co-formulation opportunities for siRNA delivery

A new approach to the synthesis of amphiphilic beta-cyclodextrins has used 'click' chemistry to selectively modify the secondary 2-hydroxyl group. The resulting extended polar groups can be either polycationic or neutral PEGylated groups and these two amphiphile classes are compatible in dual cyclodextrin formulations for delivery of siRNA. When used alone with an siRNA, a cationic cyclodextrin was shown to have good transfection properties in cell culture. Co-formulation with a PEGylated cyclodextrin altered the physicochemical properties of nanoparticles formed with siRNA. Improved particle properties included lower surface charges and reduced tendency to aggregate. However, as expected, the transfection efficiency of the cationic vector was lowered by co-formulation with the PEGylated cyclodextrin, requiring future surface modification of particles with targeting ligands for effective siRNA delivery

Cationic and PEGylated amphiphilic cyclodextrins: co-formulation opportunities for neuronal siRNA delivery

Optimising non-viral vectors for neuronal siRNA delivery presents a significant challenge. Here, we investigate a co-formulation, consisting of two amphiphilic cyclodextrins (CDs), one cationic and the other PEGylated, which were blended together for siRNA delivery to a neuronal cell culture model. Co-formulated CD-siRNA complexes were characterised in terms of size, charge and morphology. Stability in salt and serum was also examined. Uptake was determined by flow cytometry and toxicity was measured by MTT assay. Knockdown of a luciferase reporter gene was used as a measure of gene silencing efficiency. Incorporation of a PEGylated CD in the formulation had significant effects on the physical and biological properties of CD. siRNA complexes. Co-formulated complexes exhibited a lower surface charge and greater stability in a high salt environment. However, the inclusion of the PEGylated CD also dramatically reduced gene silencing efficiency due to its effects on neuronal uptake. The co-formulation strategy for cationic and PEGylated CDs improved the stability of the CD. siRNA delivery systems, although knockdown efficiency was impaired. Future work will focus on the addition of targeting ligands to the co-formulated complexes to restore transfection capabilities

Genome sequence of jumbo phage vB_AbaM_ME3 of Acinetobacter baumanni

Bacteriophage (phage) vB_AbaM_ME3 was previously isolated from wastewater effluent using the propagating host Acinetobacter baumannii DSM 30007. The full genome was sequenced, revealing it to be the largest Acinetobacter bacteriophage sequenced to date with a size of 234,900 bp and containing 326 open reading frames (ORFs)

Click-modified cyclodextrins as non-viral vectors for neuronal siRNA delivery

RNA interference (RNAi) holds great promise as a strategy to further our understanding of gene function in the central nervous system (CNS) and as a therapeutic approach for neurological and neurodegenerative diseases. However, the potential for its use is hampered by the lack of siRNA delivery vectors, which are both safe and highly efficient. Cyclodextrins have been shown to be efficient and low toxicity gene delivery vectors in various cell types in vitro. However, to date they have not been exploited for delivery of oligonucleotides to neurons. To this end, a modified β-cyclodextrin (CD) vector was synthesised, which complexed siRNA to form cationic nanoparticles of less than 200nm in size. Furthermore, it conferred stability in serum to the siRNA cargo. The in vitro performance of the CD in both immortalised hypothalamic neurons and primary hippocampal neurons was evaluated. The CD facilitated high levels of intracellular delivery of labelled siRNA, whilst maintaining at least 80% cell viability. Significant gene knockdown was achieved, with a reduction in luciferase expression of up to 68% and a reduction in endogenous glyceraldehyde phosphate dehydrogenase (GAPDH) expression of up to 40%. To our knowledge, this is the first time that a modified CD has been used as a safe and efficacious vector for siRNA delivery into neuronal cells