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Thursday, October 23, 2014
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Evaluation Of Single Point And IC50 Shift Assays For Measuring Time-Dependent Inhibition Of Drug Discovery Compounds
Katie Fox, Rosey Pearson, Phillip Butler, Clive Dilworth

The aim of this study is to evaluate different assay designs, and data analysis methodology for measuring the extent of TDI for known inhibitors. We propose a reversible inhibition and TDI screening platform to cover early phase compounds, which enables accurate decisions to be made regarding development of compounds which could cause DDIs.

Nitric Oxide Decreases the Expression and Activity of the Ubiquitin-Conjugating Enzyme UbcH10
Nick D. Tsihlis, PhD, Chris S. Oustwani, BA, Ashley K. Vavra, MD, Qun Jiang, MD and Melina R. Kibbe, MD

Nitric oxide (NO) has been shown to limit the formation of neointimal hyperplasia in animal models of arterial injury. Ubiquitination proceeds via formation of thioester bonds and NO can act to disrupt those bonds. We report that NO decreases the activity and expression of UbcH10 in vitro, and decreases the expression of UbcH10 following arterial injury in vivo. Therefore, UbcH10 may be a promising therapeutic target for inhibiting neointimal hyperplasia.

SuperNatural: A Database of Available Natural Compounds
Melanie Füllbeck, Mathias Dunkel and Robert Preissner

The majority of marketed drugs are natural compounds or derivatives thereof. The compounds availability is often unclear. Therefore we have compiled a database of ~50,000 natural compounds. Starting point for in silico screenings are about 2,500 well-known, classified natural compounds or imported molecules. Possible medical applications can be detected and about three million conformers computed to account for the flexibility during usage of the 3D-superposition algorithm.

Microwave chemistry in SiC Reaction Vials
D. Obermayer, B. Gutmann, B. Reichart, C. O. Kappe

Using novel SiC-technology to mimic conventional heated autoclave experiments.

Enzyme kinetic measurements performed on BMG LABTECH´s FLUOstar OPTIMA

BMG LABTECH has developed a new evaluation software feature able to calculate the Km value as well as the maximal velocity (Vmax) from an enzymatic kinetic measurement. Enzymes differ in their affinity to specific substrates and this affinity is represented by the Michaelis-Menten constant Km. The new software feature for enzyme kinetic offers fast and easy calculation of Km and Vmax. Available plots are the common Michaelis-Menten, Lineweaver-Burk, Eadie-Hofstee, Scatchard and Hanes kinetic f

Automated Microreactor Optimisation of the Swern-Moffatt Oxidation at Elevated Temperatures
Pieter J. Nieuwland, Kaspar Koch, Noud van Harskamp, Ron Wehrens, Jan C.M. van Hest and Floris P.J.T. Rutjes

Optimisation of the selective Swern-Moffatt oxidation of benzyl alcohol to benzaldehyde by varying five experimental parameters in an automated microreactor setup.

Organic azide synthesis in microreactors: from optimization to lab scale production
Pieter J. Nieuwland, Bo Hanssen, Kaspar Koch, Paul Janssen, Marielle M.E. Delville, Anton Lunshof and Floris P.J.T. Rutjes

The formation of benzyl azide by diazotransfer to benzyl amine was screened and subsequently scaled up using continuous flow chemistry.

Five noncovalent peptidic ligands show different affinity rankings in solution and gas phase
Andrey Dyachenko , Michael Goldflam , Marta Vilaseca , Ernest Giralt

Stability of noncovalent complexes of VEGF protein with 5 peptidic ligands is studied. Experiments were conducted in solution (NMR CSP, ITC) and in gas phase (CID TOF MS). Each ligand differs from others in chirality of one amino acid. It was shown, that trend of stability of the studied noncovalent complexes is reversed in the gas phase relatively to the solution. An explanation of this behavior is presented.

Synthesis and trafficking of the tonoplast potassium channel AtTPK1
Marie Maitrejean (1,2), Michael Wudick (2), Camilla Voelker (2), Katrin Czempinski (2), Emanuela Pedrazzini (1), Alesandro Vitale (1)

Sorting signals of tonoplast proteins and the pathway they follow through the endomembrane system are still poorly characterized. Using Brefeldin A (an inhibitor of the Golgi-mediated traffic) we showed that a Golgi-dependent pathway for tonoplast delivery may exist. Then we generated various chimeric TPK1-TPK4 fusions, exchanging various domains. We observed that the cytosolic, C-terminal domain of TPK1 is sufficient to re-direct the plasma membrane TPK4 to the tonoplast.

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Showing Results 61 - 70 of 159
Scientific News
Misfolded Proteins Clump Together in a Surprising Place
Stowers researchers create new framework for protein aggregation under acute stress.
Nanoparticle Research Could Enhance Drug Delivery Through Skin
A milestone study from the University of Southampton could have major implications for the delivery of drugs.
Chemists Recruit Anthrax to Deliver Cancer Drugs
With some tinkering, a deadly protein becomes an efficient carrier for antibody drugs.
Protein ‘Map’ Could Lead to Potent New Cancer Drugs
Findings will help scientists to design drugs that could target NMT enzyme.
Animal Testing can Mislead Drug Discovery and Development
Several blockbuster drugs would not be on the market, if scientists had relied solely on drug-uptake in animal trials, according to new research.
Synthesis and Bioactivity of Analogues of Tropodithietic Acid
The study suggests that the sulfur atoms in the marine antibiotic TDA are not essential for bioactivity, but different modes of action for TDA and its sulfur-free analogue cannot be excluded.
Cancer-Fighting Drugs Might Also Stop Malaria Early
A number of compounds have been identified which could be used to fight malaria.
Collaboration Leads to Possible Shortcut to New Drugs
The reaction, reported in Science, demonstrates how a carboxylic acid can be transformed into a very reactive site through use of a novel photoredox catalyst.
Catalysts That Mimic Enzymes Could Revolutionize Pharmaceutical Manufacturing
Structures made of polymer chains allow the catalysts to work in water.
Discovery of How Taxol Works Could Lead to Better Anticancer Drugs
The drug’s interference with the normal function of microtubules could help in designing better anticancer drugs.
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