Chemistry

Here, we report on a novel, versatile approach for the preparation of mediated enzyme electrodes, demonstrated using cross-linked films of glucose oxidase and a range of functionalised osmium complexes on graphite electrodes. Response of enzyme electrodes are optimised by evaluation of glucose response as a function of variation in ratios of [Os (2,2′-bipyridine) 2 (4-aminomethyl pyridine)Cl] + redox mediator, polyallylamine support and glucose oxidase enzyme cross-linked using a di-epoxide reagent in films on graphite. Lowering of the redox potential required to mediate glucose oxidation is achieved by synthesis of complexes using (4,4′dimethyl-2,2′-bipyridine) or (4,4′-dimethoxy-2,2′-bipyridine) as a ligand instead of (2,2′-bipyridine). Enzyme electrodes prepared using the complexes based on dimethoxyor dimethyl-substituted bipyridines provide glucose oxidation current densities of 30 and 70 μAcm −2 at 0.2 and 0.35 V applied potential compared to 120 μA cm −2 at 0.45 V for the initial enzyme electrode, under pseudophysiological conditions in 5 mM glucose, with stability of signals proving inadequate for long-term operation. Current output and stability may be improved by selection of alternate anchoring and cross-linking methodology, to provide enzyme electrodes capable for application to long-term glucose biosensors and anodes in enzymatic fuel cells.

The sugar oxidising enzymes glucose oxidase, glucose dehydrogenases (GDH) and cellobiose dehydrogenases (CDH) were co-immobilised, in the presence of multiwalled carbon nanotubes, with osmium redox polymers. Under pseudo-physiological conditions of 5 mM glucose, 150 mM NaCl, 37 8C, glucose oxidation current densities above 800 mA cm À2 are obtained from films containing an [Os(4,4'-dimethyl-2,2'-bipyridine) 2 (poly-vinylimidazole) 10 Cl] + redox polymer, redox potential 0.1 V vs. Ag/AgCl, and either glucose oxidase or FAD-dependant GDH. Current produced by, and stability of, glucose-oxidising half-cells is compared in 100 mM glucose, with films containing CDHs proving most stable. Such results show promise for development of glucose-oxidising enzymatic fuel cells.

The synthesis of a series of chiral hydroxy amide ligands is described. These ligands were used in a ruthenium-catalysed transfer hydrogenation reaction where one ligand gave the product in 72% ee. The ligands were also used in two titanium-catalysed reactions, an alkylation where ee's of up to 74% were achieved and a phenyl acetylene addition where more modest selectivities were observed.

In this work, hydrogen peroxide decomposition and oxidation of organics in aqueous medium were studied in the presence of activated carbon prepared from wet blue leather waste. The wet blue leather waste, after controlled pyrolysis under CO 2 flow, was transformed into chromium-containing activated carbons. The carbon with Cr showed high microporous surface area (up to 889 m 2 g −1 ). Moreover, the obtained carbon was impregnated with nanoparticles of chromium oxide from the wet blue leather. The chromium oxide was nanodispersed on the activated carbon, and the particle size increased with the activation time. It is proposed that these chromium species on the carbon can activate H 2 O 2 to generate HO • radicals, which can lead to two competitive reactions, i.e. the hydrogen peroxide decomposition or the oxidation of organics in water. In fact, in this work we observed that activated carbon obtained from leather waste presented high removal of methylene blue dye combining the adsorption and oxidation processes.

1,5-Dideoxy-1,5-imino-L-fucitol (1-deoxyfuconojirimycin, DFJ) is an iminosugar that inhibits fucosidases. Herein, N-alkyl DFJs have been synthesised and tested against the α-fucosidases of T. maritima (bacterial origin) and B. taurus (bovine origin). The Nalkyl derivatives were inactive against the bacterial fucosidase, while inhibiting the bovine enzyme. Docking of inhibitors to homology models, generated for the bovine and human fucosidases, was carried out. N-Decyl-DFJ was toxic to cancer cell lines and was more potent than the other N-alkyl DFJs studied.

Advancements in understanding of the genetics, genomics, biochemistry and the pharmacology of cancer in human, have driven the current cancer chemotherapy to intently focus on development of target-based approaches rather than conventional approaches. From among the various targets identified, validated and inhibited at different hallmarks of cancer, protein tyrosine kinases (PTKs) have been exploited the most. Insulin receptors (IRs), insulin like growth factor receptors (IGF-1R) and their hybrid receptors belong to tyrosine kinase receptor (TKR) family, constitute a structural homology among them and generate a growth promoting IGF system on binding with either insulin, IGF-1 or IGF-2. The system induces the mitogenic effects through a torrent of cell signals produced as a result of cross talk with other growth promoting peptides and steroidal hormones, ultimately resulting in hijacking apoptosis and increasing cell proliferation and cell survival in cancer cells. Various strategies such as anti-IGF-1R antibodies, IGF-1 mimetic peptides, antisense strategies, IGF-1R specific peptide aptamers, targeted degradation of IGF-1R and expression of dominant negative IGF-1R mutants have been explored to inhibit the IGF-1R signaling. However, targeting IGF-1R with small molecules has gained considerable attention in last few years due to their ease of synthesis, ease of optimization of absorption, distribution, metabolism, excretion and toxicity (ADMET) parameters, oral route of administration, lesser side effects and cost effectiveness. The present review provides a broad overview and discusses the highlights on discoveries, SAR studies and binding interactions of small molecules with either IGF-1R active or allosteric sites reported till date.

Cystathionineβ-lyase-like protein (CBLP), one of the key enzymes involved in methionine biosynthesis utilising pyridoxal phosphate (PLP) as a cofactor, has recently been reported inLeishmania major. Its presence in the parasite and absence in humans warrant its full characterisation and fruition as a potent, selective, and inevitable druggable target. Due to the unavailability of X-ray 3D structure of CBLP, a homology model for this protein was developed for the first time. The model was evaluated for PLP binding site and various conserve domain residues of the protein recommended by comparative sequence analyses by different protein analysis tools. The model was validated and discovered to be robust and statistically significant. The final model was superimposed on template ofArabidopsis thaliana(PDB ID: 1IBJ) and RMSD was found to be 0.486. The PLP binding site residues of both the proteins were ensued to be highly conserved indicated by Gly71, Met72, Tyr95, Asp169, and Ser193 as ...

Activation of immune response is developed in respect to some xenobiotic sensitization, which is supposed to prevent and protect the body from sufferings induced by these xenobiotic. But unfortunately sometime body behaves in a paradoxical manner which misguides the immune system and ultimately turned into a bizarre situation of immune function. One of such response is anaphylactic shock, which is quite fatal if untreated. This review brings insights into the molecular physiology of anaphylactic shock and how some people elicit allergic response to certain substances but not the other. This major catastrophe of the body holds an error of immune system whereas this commentary based review disclosed the synchronization of the unfortunate lessons of the immune system, which makes it a cruel to cause DEATH!

Stereochemistry of clinical agents play a key role in their success to become drugs. Tautomerism is a structural isomerism, playing a key role in the orientation of organic compounds and also found significant in distinctive base pairing in nucleic acids. Keto-enol form usually occurs and found prominently among different types of tautomers. The enolform ionizes in the physiological solution into enolate and alter the biological activity. So, how this enolate form brings modification in pharmacokinetics and pharmacodynamics of a drug is very important and quite interesting to know. As this form is ionic in nature so it increases the interaction with the concerning receptors, enzymes, ion channels or functional proteins. In this review we cover and compile success, role and the significance of the enolate form of clinical agents which succeed to become drugs!

Advancements in understanding of the genetics, genomics, biochemistry and the pharmacology of cancer inhuman, have driven the current cancer chemotherapy to intently focus on development of target-based approaches rather than conventional approaches. From among the various targets identified, validated and inhibited at different hallmarks of cancer, protein tyrosine kinases (PTKs) have been exploited the most. Insulin receptors (IRs), insulin like growth factor receptors (IGF-1R) and their hybrid receptors belong to tyrosine kinase receptor (TKR) family, constitute a structural homology among them and generate a growth promoting IGF system on binding with either insulin, IGF-1 or IGF-2. The system induces the mitogenic effects through a torrent of cell signals produced as a result of cross talk with other growth promoting peptides and steroidal hormones, ultimately resulting in hijacking apoptosis and increasing cell proliferation and cell survival in cancer cells. Various strategie...

A build-couple-pair strategy, including double-reductive amination macrocyclization, has been used to generate decorated macrocycles (eannaphanes) with an embedded triazole and monosaccharide. Biological screening led to the identification of an inducer of apoptosis in leukemic cells, which acts at least partially as a 5-HT2 antagonist.