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High Throughput Screening (high + throughput_screening)
Selected AbstractsHigh Throughput Screening for the Design and Optimization of Chromatographic Processes: Assessment of Model Parameter Determination from High Throughput Compatible DataCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 12 2008A. Susanto Abstract Chromatographic processes can be optimized in various ways, and the two most prominent approaches are based either on statistical data analysis or on experimentally validated simulation models. Both strategies rely heavily on experimental data, the generation of which usually imposes a significant bottleneck on rational process design. The latter approach is followed in this work, and the utilizability of high throughput compatible experiments for the determination of model parameters which are required for in silico process optimization, is assessed. The unknown parameter values are estimated from batch uptake experiments on a robotic platform and from dynamic breakthrough experiments with miniaturized chromatographic columns. The identified model is then validated with respect to process optimization by comparison of model predictions with experimental data from a preparative scale column. In this study, a strong cation exchanger Toyopearl SP-650M and lysozyme solved in phosphate buffer (pH 7), is used as the test system. The utilization of data from miniaturized and high throughput compatible experiments is shown to yield sufficiently accurate results, and minimizes efforts and costs for both parameter estimation and model validation. [source] High Throughput Screening Identifies Novel Inhibitors of Escherichia coli Dihydrofolate Reductase that Are Competitive with Dihydrofolate.CHEMINFORM, Issue 43 2003Michela Zolli-Juran Abstract For Abstract see ChemInform Abstract in Full Text. [source] Engineering Chiral Catalysts through Asymmetric Activation and Super High Throughput Screening (SHTS)CHINESE JOURNAL OF CHEMISTRY, Issue 6 2001Koichi Mkami Abstract A conceptually new strategy for asymmetric catalysis, namely asymmetric activation, in which a chiral activator selectively activates one enantiomer of a racemic chiral catalyst, and a highly efficient screening system for finding the most effective catalysts, namely super high throughput screening (SHTS), by which the reaction can be conducted in parallel and the ee% of the product is allowed to determine within minutes, are summarized in the present account. It is reasonable to believe that SHTS technique combined with asymmetric activation or deactivation principle will provide a very powerful methodology for finding the new catalysts and the best catalyst tuning for asymmetric reactions. [source] Ferrocenyl-Aryl Based trans -Chelating Diphosphine Ligands: Synthesis, Molecular Structure and Application in Enantioselective HydrogenationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6 2010Raffael Schuecker Abstract Potentially trans -chelating diphosphine ligands based on a ferrocenyl-aryl backbone were synthesised in a four-step sequence and the molecular structures in the solid state of two representatives were determined by X-ray diffraction. High throughput screening of these ligands in rhodium-, ruthenium- and iridium-mediated hydrogenations of a variety of alkenes and ketones revealed that these ligands can deliver high enantioselectivity for alkenes (up to 98% ee) but are less selective when ketones are used as the substrates. The coordination behaviour of one ligand in its square planar palladium and platinum dichloride complexes was studied by 31P,NMR and only trans -chelated complexes, together with oligomeric by-products, were observed. Reaction with the (p -cymene)ruthenium dichloride dimer, [RuCl2(p -cymene)]2, resulted in a mixture of diastereomeric complexes. [source] Selective Oxidation of Alcohols to Carbonyl Compounds and Carboxylic Acids with Platinum Group Metal CatalystsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 4 2003Ross Anderson Abstract The use of platinum group metal (PGM) catalysts for the selective oxidation of various primary and secondary alcohols under mild conditions is described. High throughput screening (HTS) techniques have been used to identify trends in catalyst activity and product selectivity. Using air as oxidant and water as solvent 5% Pt, 1% Bi/C has been identified as an efficient catalyst for the transformation of 2-octanol to 2-octanone and 1-octanol to octanoic acid. To improve aldehyde selectivity the promotion of Pt/Al2O3 and Ru/C catalysts has been investigated. The use of H2O2 as oxidant has been demonstrated as a suitable alternative to air. [source] Computational analysis of the cathepsin B inhibitors activities through LR-MMPBSA binding affinity calculation based on docked complexJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 14 2009Zhigang Zhou Abstract Cathepsin B, a ubiquitous lysosomal cysteine protease, is involved in many biological processes related to several human diseases. Inhibitors targeting the enzyme have been investigated as possible diseases treatments. A set of 37 compounds were recently found active in a high throughput screening assay to inhibit the catalytic activity of Cathepsin B, with chemical structures and biological test results available to the public in the PubChem BioAssay Database (AID 820). In this study, we compare these experimental activities to the results of theoretical predictions from binding affinity calculation with a LR-MM-PNSA approach based on docked complexes. Strong correlations (r2 = 0.919 and q2 = 0.887 for the best) are observed between the theoretical predictions and experimental biological activity. The models are cross-validated by four independent predictive experiments with randomly split compounds into training and test sets. Our results also show that the results based on protein dimer show better correlations with experimental activity when compared to results based on monomer in the in silico calculations. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009 [source] Electric field controlled electrospray deposition for precise particle pattern and cell pattern formationAICHE JOURNAL, Issue 10 2010Jingwei Xie Abstract Photolithography, soft lithography, and ink jetting have been used for automated micropattern fabrication. However, most of the methods for microfabrication of surface pattern are limited to the investigation of material properties of substrates with high-cost and complex procedures. In the present study, we show a simple (single-step) yet versatile and robust approach to generate biodegradable polymeric particle patterns on a substrate using electrospray deposition through a mask. Various particle patterns including patterned dots, circles, squares, and bands can be easily formed and the features of particle patterns could also be tailored using different masks and electrostatic focusing effects. Furthermore, cell patterns can be achieved on the surface of particle patterns by blocking the areas without particle deposition on the substrate and culturing cells on the substrate. Polymeric particle patterns and cell patterns developed in this study could be used in the high throughput screening of sustained release formulations, cell-based sensing, and drug discovery. In addition to experimental results, an analysis of the associated electric field is used to investigate quantitatively the nature of focusing effect. Scaling analysis is also applied to obtain the dominate terms in electrospray deposition process. © 2010 American Institute of Chemical Engineers AIChE J, 2010 [source] Feasibility studies on a protein kinase assay when using radioisotope detection technique for developing a protein biochipJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2007Sang Hyun Park Abstract Microarrays have recently become a precious research tool for proteomics and clinical investigation. Their applications to the diagnosis of a disease have emerged as a significant promise for medical advances. In this study, we report on an efficient strategy for the detection of phosphorylation of a substrate catalyzed by kinase, using the radioisotope (RI) detection technique for a protein biochip. This technique does not employ the use of the blocking step which is commonly used in conventional methods to prevent non-specific binding. It was found that the usage of a RI detection technique has the advantages of being highly sensitive and time saving when compared with other conventional methods. The results can be applied when using RI detection technique to develop biochips to determine the activity of a protein kinase. Further, it can be a useful tool for a high throughput screening and for studying protein,protein interactions. Copyright © 2007 John Wiley & Sons, Ltd. [source] Dendritic macromers for hydrogel formation: Tailored materials for ophthalmic, orthopedic, and biotech applicationsJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 2 2008Mark W. Grinstaff Abstract Dendritic macromolecules are well-defined highly branched macromolecules synthesized via a divergent or convergent approach. A salient feature of the macromolecules described herein, and a goal of our research effort, is to prepare dendritic macromolecules suitable for in vitro and in vivo use by focusing on biocompatible building blocks and biodegradable linkages. These dendritic macromolecules can be subsequently crosslinked to form hydrogels using a photochemical acrylate-based or a chemical ligation strategy. The properties,mechanical, swelling, degradation, and so forth,of the hydrogels can be tuned by altering the composition, crosslinking chemistry, wt %, generation number and so forth. The utility and diverse applicability is demonstrated through successful use of these hydrogels in three unique applications: hydrogel adhesives for repairing corneal wounds, hydrogel scaffolds for cartilage tissue engineering, and hydrogel reaction chambers for high throughput screening of molecular recognition events. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 383,400, 2008. [source] Selection criteria for drug-like compoundsMEDICINAL RESEARCH REVIEWS, Issue 3 2003Ingo Muegge Abstract The fast identification of quality lead compounds in the pharmaceutical industry through a combination of high throughput synthesis and screening has become more challenging in recent years. Although the number of available compounds for high throughput screening (HTS) has dramatically increased, large-scale random combinatorial libraries have contributed proportionally less to identify novel leads for drug discovery projects. Therefore, the concept of ,drug-likeness' of compound selections has become a focus in recent years. In parallel, the low success rate of converting lead compounds into drugs often due to unfavorable pharmacokinetic parameters has sparked a renewed interest in understanding more clearly what makes a compound drug-like. Various approaches have been devised to address the drug-likeness of molecules employing retrospective analyses of known drug collections as well as attempting to capture ,chemical wisdom' in algorithms. For example, simple property counting schemes, machine learning methods, regression models, and clustering methods have been employed to distinguish between drugs and non-drugs. Here we review computational techniques to address the drug-likeness of compound selections and offer an outlook for the further development of the field. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 3, 302-321, 2003 [source] Current recommendations for the molecular evaluation of newly diagnosed holoprosencephaly patients,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Daniel E. Pineda-Alvarez§ Abstract Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans and is typically characterized by different degrees of hemispheric separation that are often accompanied by similarly variable degrees of craniofacial and midline anomalies. HPE is a classic example of a complex genetic trait with "pseudo"-autosomal dominant transmission showing incomplete penetrance and variable expressivity. Clinical suspicion of HPE is typically based upon compatible craniofacial findings, the presence of developmental delay or seizures, or specific endocrinological abnormalities, and is then followed up by confirmation with brain imaging. Once a clinical diagnosis is made, a thorough genetic evaluation is necessary. This usually includes analysis of chromosomes by high-resolution karyotyping, clinical assessment to rule-out well recognized syndromes that are associated with HPE (e.g., Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome and others), and molecular studies of the most common HPE associated genes (e.g., SHH, ZIC2 and SIX3). In this review, we provide current step-by-step recommendations that are medically indicated for the genetic evaluation of patients with newly diagnosed HPE. Moreover, we provide a brief review of several available methods used in molecular diagnostics of HPE and describe the advantages and limitations of both currently available and future tests as they relate to high throughput screening, cost, and the results that they may provide. Published 2010 Wiley-Liss, Inc. [source] A high throughput drug screen based on fluorescence resonance energy transfer (FRET) for anticancer activity of compounds from herbal medicineBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2007H Tian Background and purpose: We report the development of a very efficient cell-based high throughput screening (HTS) method, which utilizes a novel bio-sensor that selectively detects apoptosis based on the fluorescence resonance energy transfer (FRET) technique. Experimental approach: We generated a stable HeLa cell line expressing a FRET-based bio-sensor protein. When cells undergo apoptosis, they activate a protease called ,caspase-3'. Activation of this enzyme will cleave our sensor protein and cause its fluorescence emission to shift from a wavelength of 535 nm (green) to 486 nm (blue). A decrease in the green/blue emission ratio thus gives a direct indication of apoptosis. The sensor cells are grown in 96-well plates. After addition of different chemical compounds to each well, a fluorescence profile can be measured at various time-points using a fluorescent plate reader. Compounds that can trigger apoptosis are potential candidates as anti-cancer drugs. Key results: This novel cell-based HTS method is highly effective in identifying anti-cancer compounds. It was very sensitive in detecting apoptosis induced by various known anti-cancer drugs. Further, this system detects apoptosis, but not necrosis, and is thus more useful than the conventional cell viability assays, such as those using MTT. Finally, we used this system to screen compounds, isolated from two plants used in Chinese medicine, and identified several effective compounds for inducing apoptosis. Conclusions and Implications: This FRET-based HTS method is a powerful tool for identifying anti-cancer compounds and can serve as a highly efficient platform for drug discovery. British Journal of Pharmacology (2007) 150, 321,334. doi:10.1038/sj.bjp.0706988 [source] Engineering Chiral Catalysts through Asymmetric Activation and Super High Throughput Screening (SHTS)CHINESE JOURNAL OF CHEMISTRY, Issue 6 2001Koichi Mkami Abstract A conceptually new strategy for asymmetric catalysis, namely asymmetric activation, in which a chiral activator selectively activates one enantiomer of a racemic chiral catalyst, and a highly efficient screening system for finding the most effective catalysts, namely super high throughput screening (SHTS), by which the reaction can be conducted in parallel and the ee% of the product is allowed to determine within minutes, are summarized in the present account. It is reasonable to believe that SHTS technique combined with asymmetric activation or deactivation principle will provide a very powerful methodology for finding the new catalysts and the best catalyst tuning for asymmetric reactions. [source] | ||||||||||