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Chemical Approach (chemical + approach)
Kinds of Chemical Approach Selected AbstractsChemical Approach for the Study of the ,Kissing Complex' of Moloney murine leukaemia VirusHELVETICA CHIMICA ACTA, Issue 7 2008Sébastien Porcher Abstract The replication of Moloney murine leukaemia virus relies on the formation of a stable homodimeric ,kissing complex' of a GACG tetraloop interacting through only two C,G base pairs flanked of 5,-adjacent unpaired adenosines A9. Previous NMR investigations of a model stem loop 1 has not permitted to reveal the origin of this interaction. Therefore, with the aim of deeper comprehension of the phenomena, the model sequence 10 was prepared where position 9 has been substituted for a nucleoside offering a wider , -stacking. In this context, the wyosine phosphoramidite building block 2 was prepared and incorporated by adapting the conditions of the automated synthesis and developing original templated enzymatic ligation. However, no ,kissing interaction' has been observed for this model sequence 10 due to steric hindrance as confirmed by computational simulation. Consequently, several other model sequences, 18, 23,26, containing modified nucleosides were prepared. Finally, the importance of the cross-loop H-bond between G8 and G11 nucleobases was revealed by preparing a 18mer RNA hairpin 27, where the guanosine G8 has been substituted for inosine. The latter, which does not possess a C3 amino function compared to guanosine, is unable to form any ,kissing complex' demonstrating the importance of this secondary interaction in the formation of the complex. [source] A Chemical Approach Towards Understanding the Mechanism and Reversal of Drug Resistance in Plasmodium falciparum: Is it Viable?IUBMB LIFE, Issue 4-5 2002Kelly Chibale Abstract Genetic and biochemical approaches to studies of drug resistance mechanisms in Plasmodium falciparum have raised controversies and contradictions over the past several years. A different and novel chemical approach to this important problem is desirable at this point in time. Recently, the molecular basis of drug resistance in P. falciparum has been associated with mutations in the resistance genes, Chloroquine Resistance Transporter (PfCRT) and the P-glycoprotein homologue (Pgh1). Although not the determinant of chloroquine resistance in P. falciparum, mutations in Pgh1 have important implications for resistance to other antimalarial drugs. Because it is mutations in the aforementioned resistance genes rather than overexpression that has been associated with drug resistance in malaria, studies on mechanisms of drug resistance and its reversal by chemosensitisers should benefit from a chemical approach. Target-oriented organic synthesis of chemosensitisers against proteins implicated in drug resistance in malaria should shed light on mechanism of drug resistance and its reversal in this area. The effect of structurally diverse chemosensitisers should be examined on several putative resistance genes in P. falciparum to deal with antimalarial drug resistance in the broadest sense. Therefore, generating random mutations of these resistance proteins and subsequent screening in search of a specific phenotype followed by a search for mutations and/or chemosensitisers that affect a specific drug resistance pathway might be a viable strategy. This diversity-oriented organic synthesis approach should offer the means to simultaneously identify resistance proteins that can serve as targets for therapeutic intervention (therapeutic target validation) and chemosensitisers that modulate the functions of these proteins (chemical target validation). [source] Hydrodenitrification with PdCu Catalysts: Catalyst Optimization by Experimental and Quantum Chemical ApproachesISRAEL JOURNAL OF CHEMISTRY, Issue 1 2006Irena Efremenko A continuous process for nitrate and nitrite abatement from drinking water by catalytic hydrogenation has been developed in our lab. We describe the experimental process development procedure, and support it with semiempirical quantum chemical methods. Comparisons of activated carbon (ACC) and silica glass fiber (GFC) cloths as supports for mono- and bimetallic Pd-Cu catalysts show the former to be 45-fold and 15-fold more active for nitrite and nitrate hydrogenation, respectively, than the latter. Catalysts prepared by selective deposition of Cu on Pd/ACC led to better activity for nitrate hydrogenation than catalysts prepared by co-impregnation or ion exchange methods. The optimal Cu:Pd atomic ratio was found to be 1:2. The computational results show the following: (i) The dispersion of Pd catalysts supported on ACC is much higher than that on GFC due to the larger surface area and higher density of adsorption sites, and that accounts for the higher activity of PdCu/ACC; (ii) Nanosized Pd particles supported on ACC have a semispherical shape and possess preferentially close-packed triangular surfaces, while Pd/GFC particles are extended in the direction parallel to the support surface and show both fcc (100) and (111) planes; (iii) The interaction of Cu atoms with both supports is stronger than that of Pd; adsorbed Cu atoms show a greater ability to form monometallic than bimetallic bonds and that should result in poor mixing of the metal upon co-impregnation, as was observed experimentally; (iv) Cu atoms in bimetallic PdCu particles admit a significant positive charge; the experimentally measured solubility of metal atoms correlates with their calculated charges. The best catalyst (2 wt%Pd-0.6 wt%Cu/ACC) was employed in a novel continuous flow reactor for nitrate hydrogenation in distilled and tap water. The advantages of the reactor investigated over a conventional packed bed reactor are discussed, suggesting a potential for further process intensification. [source] Chemical Approaches to Controlling Intracellular Protein DegradationCHEMBIOCHEM, Issue 1 2005John S. Schneekloth Jr. Inactive. Recent advances have yielded many ways to study proteins by means of inactivation. Traditional methods of genetic knockout are complimented by newer techniques, including RNAi and small molecules that induce proteolysis (see scheme). Although seemingly in competition, these techniques each offer solutions to specific problems in proteomic analysis. [source] Cover Picture: A Fusion of Disciplines: Chemical Approaches to Exploit Fusion Proteins for Functional Genomics (ChemBioChem 9/2003)CHEMBIOCHEM, Issue 9 2003Nils Johnsson Abstract The cover picture shows a living cell inside which a protein is labeled with fluorescein. The labeling is based on the unusual mechanism of the DNA repair protein O6 -alkylguanine-DNA alkyltransferase (AGT, structure on the right), which irreversibly transfers the alkyl group from O6 -alkylguanine to its reactive cysteine residue. By using O6 -benzylguanine derivatives such as the fluorescein derivative shown, AGT fusion proteins can be covalently labeled in vivo. The method is one example of a growing number of approaches that aim at equipping proteins with functionalities that can not be genetically encoded, which opens up new ways to study proteins in vivo. Further information can be found in the article by N. Johnsson and K. Johnsson on p. 803,ff. [source] Click Chemistry-Led Advances in High Content Functional ProteomicsMOLECULAR INFORMATICS, Issue 11-12 2007Abstract The availability of complete genome sequences for numerous eukaryotic and prokaryotic organisms has inspired the advent of new methods to functionally characterize proteins on a global scale. Chemical approaches, in particular, have emerged as a powerful way to investigate the proteome, providing small-molecule probes that report on protein activity and Post-Translational Modification (PTM) state directly in complex biological samples. Many of the key advances made in chemical proteomics can be attributed to the development of efficient bio-orthogonal reactions such as the copper (I)-catalyzed Huisgen's azide,alkyne cycloaddition, a reaction commonly known as "Click Chemistry" (CC). The generation of "clickable" proteomics probes has removed the requirement for bulky reporter tags, thereby allowing access to more biologically relevant systems such as live cells or animals. The versatility of CC has also allowed for greater experimental efficiency, as different reporter tags (i.e., a fluorophore for detection or biotin for enrichment) can be appended to a single probe. Such advances have enabled researchers to identify protein activities dysregulated in disease states, assess the selectivity of enzyme inhibitors in vivo, and inventory specific PTMs on a proteome-wide scale. [source] Colloidal-Crystal-Assisted Patterning of Crystalline MaterialsADVANCED MATERIALS, Issue 13 2010Cheng Li Abstract Colloidal crystals have shown great potential as versatile templates for the fabrication of patterned micro- and nanostructures with complex architectures and novel properties. The patterning of functional crystalline materials in two and three dimensions is essential to the realization of their applications in many technologically important fields. This article highlights some recent progress in the fabrication of 2D and 3D patterned crystalline materials with the assistance of colloidal crystals. By combining a bioinspired synthetic strategy based on a transient amorphous phase with a colloidal-crystal templating method, unique 3D ordered macroporous (3DOM) calcite single crystals can be created. Moreover, patterned arrays of regular ZnO nanopillars with controlled size, shape, and orientation can be fabricated via a facile wet chemical approach by using masks derived from monolayer colloidal crystals (MCC). [source] A Chemical Approach Towards Understanding the Mechanism and Reversal of Drug Resistance in Plasmodium falciparum: Is it Viable?IUBMB LIFE, Issue 4-5 2002Kelly Chibale Abstract Genetic and biochemical approaches to studies of drug resistance mechanisms in Plasmodium falciparum have raised controversies and contradictions over the past several years. A different and novel chemical approach to this important problem is desirable at this point in time. Recently, the molecular basis of drug resistance in P. falciparum has been associated with mutations in the resistance genes, Chloroquine Resistance Transporter (PfCRT) and the P-glycoprotein homologue (Pgh1). Although not the determinant of chloroquine resistance in P. falciparum, mutations in Pgh1 have important implications for resistance to other antimalarial drugs. Because it is mutations in the aforementioned resistance genes rather than overexpression that has been associated with drug resistance in malaria, studies on mechanisms of drug resistance and its reversal by chemosensitisers should benefit from a chemical approach. Target-oriented organic synthesis of chemosensitisers against proteins implicated in drug resistance in malaria should shed light on mechanism of drug resistance and its reversal in this area. The effect of structurally diverse chemosensitisers should be examined on several putative resistance genes in P. falciparum to deal with antimalarial drug resistance in the broadest sense. Therefore, generating random mutations of these resistance proteins and subsequent screening in search of a specific phenotype followed by a search for mutations and/or chemosensitisers that affect a specific drug resistance pathway might be a viable strategy. This diversity-oriented organic synthesis approach should offer the means to simultaneously identify resistance proteins that can serve as targets for therapeutic intervention (therapeutic target validation) and chemosensitisers that modulate the functions of these proteins (chemical target validation). [source] Heuristic molecular lipophilicity potential (HMLP): Lipophilicity and hydrophilicity of amino acid side chainsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2006Qi-Shi Du Abstract Heuristic molecular lipophilicity potential (HMLP) is applied in the study of lipophilicity and hydrphilcity of 20 natural amino acids side chains. The HMLP parameters, surface area Si, lipophilic indices Li, and hydrophilic indices Hi of amino acid side chains are derived from lipophilicity potential L(r). The parameters are correlated with the experimental data of phase-transferring free energies of vapor-to-water, vapor-to-cyclohexane, vapor-to-octanol, cyclohexane-to-water, octanol-to-water, and cyclohexane-to-octanol through a linear free energy equation ,G°tr,i = b0 + b1Si+ + b2Si, + b3Li + b4Hi. For all above six phase-transfer free energies, the HMLP parameters of 20 amino acid side chains give good calculation results using linear free energy equation. HMLP is an ab initio quantum chemical approach and a structure-based technique. Except for atomic van der Waals radii, there are no other empirical parameters used. The HMLP has clear physical and chemical meaning and provides useful lipophilic and hydrophilic parameters for the studies of proteins and peptides. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 685,692, 2006 [source] Rapid and selective isolation of ,-xylosidase through an activity-based chemical approachBIOTECHNOLOGY JOURNAL, Issue 2 2006Lee-Chiang Lo Dr. Abstract ,-Xylosidase is a key enzyme in the xylanolytic system with a great potential in many biotechnological applications, especially in the food as well as the pulp and paper industries. We have developed a chemical approach for the rapid screening and isolation of ,-xylosidase. Activity probe LCL-6X targeting ,-xylosidase was utilized in this study. It carries a ,-xylopyranosyl recognition head, a latent trapping device consisting of a 2-fluoromethylphenoxyl group, and a biotin reporter group. The biotin reporter group serves both as a readout device and as a tool for enriching the labeled proteins. LCL-6X could selectively label a model ,-xylosidase from Trichoderma koningii. All other bystander proteins used in this study, including phosphorylase b, BSA, ovalbumin, carbonic anhydrase, and trypsin inhibitor, gave negligible cross-labeling effect. With the assistance of streptavidin agarose beads and mass spectrophotometry for the recovery and identification of the biotinylated proteins, we demonstrated that LCL-6X could be successfully applied to identify a bi-functional enzyme with ,- L -arabinofuranosidase/,-xylosidase activity from the total protein extract of a Pichia expressing system and a prospective ,-xylosidase in the culture medium of Aspergillus fumigatus. The ,-xylosidase activities from numerous microbes were also screened using the LCL-6X probe. Preliminary results showed significant differences among these microbial sources and some distinct protein bands were observed. Thus, we have successfully developed a novel chemical probe that has potential applications in xylan-related research. [source] DNA Labeling by Ligand Inducible Secondary StructureCHEMBIOCHEM, Issue 12 2008Tao Peng Dr. Personalized medical solutions: Simple, accurate, and cost effective methods of single nucleotide polymorphism typing would be necessary for personalized medicine. Towards this end, a number of SNP typing methods have been investigated and reported. We report herein, our chemical approach to practical SNP typing based on allele-specific PCR integrated with a new concept of DNA-labeling by ligand-inducible secondary structure. [source] Engineering the prion protein using chemical synthesisCHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2001H.L. Ball Abstract: In recent years, the technology of solid-phase peptide synthesis (SPPS) has improved to the extent that chemical synthesis of small proteins may be a viable complementary strategy to recombinant expression. We have prepared several modified and wild-type prion protein (PrP) polypeptides, of up to 112 residues, that demonstrate the flexibility of a chemical approach to protein synthesis. The principal event in prion disease is the conformational change of the normal, ,-helical cellular protein (PrPC) into a ,-sheet-rich pathogenic isoform (PrPSc). The ability to form PrPSc in transgenic mice is retained by a 106 residue ,mini-prion' (PrP106), with the deletions 23,88 and 141,176. Synthetic PrP106 (sPrP106) and a His-tagged analog (sPrP106HT) have been prepared successfully using a highly optimized Fmoc chemical methodology involving DCC/HOBt activation and an efficient capping procedure with N -(2-chlorobenzyloxycarbonyloxy) succinimide. A single reversed-phase purification step gave homogeneous protein, in excellent yield. With respect to its conformational and aggregational properties and its response to proteinase digestion, sPrP106 was indistinguishable from its recombinant analog (rPrP106). Certain sequences that proved to be more difficult to synthesize using the Fmoc approach, such as bovine (Bo) PrP(90,200), were successfully prepared using a combination of the highly activated coupling reagent HATU and t -Boc chemistry. To mimic the glycosylphosphatidyl inositol (GPI) anchor and target sPrP to cholesterol-rich domains on the cell surface, where the conversion of PrPC is believed to occur, a lipophilic group or biotin, was added to an orthogonally side-chain-protected Lys residue at the C-terminus of sPrP sequences. These groups enabled sPrP to be immobilized on either the cell surface or a streptavidin-coated ELISA plate, respectively, in an orientation analogous to that of membrane-bound, GPI-anchored PrPC. The chemical manipulation of such biologically relevant forms of PrP by the introduction of point mutations or groups that mimic post-translational modifications should enhance our understanding of the processes that cause prion diseases and may lead to the chemical synthesis of an infectious agent. [source] Formation of Superoxo Species by Interaction of O2 with Na Atoms Deposited on MgO Powders: A Combined Continuous-Wave EPR (CW-EPR), Hyperfine Sublevel Correlation (HYSCORE) and DFT StudyCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2010Francesco Napoli Dr. Abstract The formation of O2, radical anions by contact of O2 molecules with a Na pre-covered MgO surface is studied by a combined EPR and quantum chemical approach. Na atoms deposited on polycrystalline MgO samples are brought into contact with O2. The typical EPR signal of isolated Na atoms disappears when the reaction with O2 takes place and new paramagnetic species are observed, which are attributed to different surface-stabilised O2, radicals. Hyperfine sublevel correlation (HYSCORE) spectroscopy allows the superhyperfine interaction tensor of O2,Na+ species to be determined, demonstrating the direct coordination of the O2, adsorbate to surface Na+ cations. DFT calculations enable the structural details of the formed species to be determined. Matrix-isolated alkali superoxides are used as a standard to enable comparison of the formed species, revealing important and unexpected contributions of the MgO matrix in determining the electronic structure of the surface-stabilised Na+O2, complexes. [source] The Formation of Large-Area Conducting Graphene-Like PlateletsCHEMISTRY - A EUROPEAN JOURNAL, Issue 33 2009Riccardo Salvio Abstract The treatment of a suspension of graphite oxide (GO) with sodium azide leads to a material that, after reduction, features amino groups at the top and bottom of the sheets. These groups react through microcontact printing with an isothiocyanate monolayer on a silicon oxide substrate to form covalent bonds that strongly attach to the particles on the surface. With ultrasonication it is possible to obtain exfoliation of the sheets that are not covalently bound to the surface leaving single-layer platelets attached to the substrate. The azido derivative can be also used to functionalize the graphene oxide with long alkylic chains through a click chemistry approach. This functionalization results in the exfoliation of this material in dimethylformamide. The novel materials were fully characterized by different techniques including IR spectroscopy, thermogravimetric analysis (TGA), scanning and transmission electron microscopy (SEM and TEM), X-Ray photoelectron spectroscopy (XPS), and solid state NMR spectroscopy. The material with amino groups, after the reduction step, is conductive with a resistivity only approximately seven times larger than that of unprocessed graphite. This implies that after reduction of the GO, the conjugated sp2 network is largely restored. We consider this to be an important step towards a chemical approach for forming conducting large-area platelet films of single-layer graphene. [source] Aerobic biodegradation of the chloroethenes: pathways, enzymes, ecology, and evolutionFEMS MICROBIOLOGY REVIEWS, Issue 4 2010Timothy E. Mattes Abstract Extensive use and inadequate disposal of chloroethenes have led to prevalent groundwater contamination worldwide. The occurrence of the lesser chlorinated ethenes [i.e. vinyl chloride (VC) and cis -1,2-dichloroethene (cDCE)] in groundwater is primarily a consequence of incomplete anaerobic reductive dechlorination of the more highly chlorinated ethenes (tetrachloroethene and trichloroethene). VC and cDCE are toxic and VC is a known human carcinogen. Therefore, their presence in groundwater is undesirable. In situ cleanup of VC- and cDCE-contaminated groundwater via oxidation by aerobic microorganisms is an attractive and potentially cost-effective alternative to physical and chemical approaches. Of particular interest are aerobic bacteria that use VC or cDCE as growth substrates (known as the VC- and cDCE-assimilating bacteria). Bacteria that grow on VC are readily isolated from contaminated and uncontaminated environments, suggesting that they are widespread and influential in aerobic natural attenuation of VC. In contrast, only one cDCE-assimilating strain has been isolated, suggesting that their environmental occurrence is rare. In this review, we will summarize the current knowledge of the physiology, biodegradation pathways, genetics, ecology, and evolution of VC- and cDCE-assimilating bacteria. Techniques (e.g. PCR, proteomics, and compound-specific isotope analysis) that aim to determine the presence, numbers, and activity of these bacteria in the environment will also be discussed. [source] Mass-selective vibrational spectroscopy of vanadium oxide cluster ionsMASS SPECTROMETRY REVIEWS, Issue 4 2007Knut R. Asmis Abstract A corner stone in the study of the size-dependent properties of cluster ions in the gas phase is their structural characterization. Over the last 10 years, significant progress has been in this research field because of significant advances in the gas phase vibrational spectroscopy of mass-selected ions. Using a combination of modern experimental and quantum chemical approaches, it is now in most cases possible to uniquely identify the geometric structure of cluster ions, based on the comparison of the experimental and simulated infrared spectra. In this article, we highlight the progress made in this research area by reviewing recent infrared photodissociation (IR-PD) experiments on small and medium sized (up to 30 atoms) vanadium oxide ions. © 2007 Wiley Periodicals, Inc., Mass Spec Rev. [source] | ||||||||||||||||||||||