|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.
|Anti-inflammatory activity of Dalbergia sissoo Roxb. heart-wood|
Ohm Devani, S. K. Lahiri, D. D. Santani, M. B. Shah
The heart-wood of Dalbergia sissoo Roxb. is reported to be used in traditional medicinal practices, of which anti-inflammatory is one. The present work evaluates the effect of the heart-wood extract on the carrageenan induced rat paw edema. The drug was found to be active at lowest of 3 doses tried. the drug can be said to posses anti-inflamatory activity but needs further evaluation of discover the pathway of the same.
|Necessity of quantum mechanics for predicting binding free energy|
Ting Zhou, Danzhi Huang, Amedeo Caflisch
We demonstrate the necessity of quantum mechanics (QM) for predicting binding free energy by comparing the results of the linear interaction energy model with continuum model (LIECE) and the equivalent model with QM (QMLIECE).
|Resorufin - a lead for a new protein kinase CK2 inhibitor |
Iben Skjøth Sandholt1, Birgitte Brinkmann Olsen1, Barbara Guerra1, Olaf-Georg Issinger1, Brigitte Boldyreff2
Screening of a natural compound library led to the identification of resorufin, as a highly selective and potent inhibitor for protein kinase CK2. Out of 52 kinases tested only CK2 was inhibited. The IC50 values determined for the CK2 holoenzymes were 1.5 µM and for the free catalytic subunits ca. 4 µM. In different cancer cell lines treatment with resorufin led to cell death and endogenous CK2 was inhibited.
|MED-SuMo and MED-Hybridise: exploit all PDB macromolecule structures to design/optimize innovative leads|
Moriaud F., Oguievetskaia K., Adcock S.A., Vorotynsev A.M., Martin L., Doppelt-Azeroual O. and Delfaud F.
Obtaining structural information on fragment-protein target is a key factor and also a major limitation. We’ve used MED-SuMo and MED-Hybridise to query and mine the PDB seeking for similar interaction surfaces. MED-portions were used to design novel scaffolds (GPCR) and decorate a given scaffold (kinase). We have analysed the scaffolds in regard to their diversity, their presence in PubChem, PDB and other libraries.
|Production of prostanoids in the plant Arabidopsis thaliana|
Maged E. Mohamed and Colin M. Lazarus.
Prostanoids originate from PGHS action on the 20-carbon polyunsaturated fatty acid: DGLA, AA and EPA. We used cDNA expression in Saccharomyces cerevisiae and enzyme immunoassays to compare the activities of two mouse PGHS isoforms and cDNAs encoding mouse prostaglandin I synthase and thromboxane A synthase and genomic DNA encoding Trypanosoma brucei prostaglandin F synthase. All genes were active and were put in Transgenic Arabidopsis thaliana plants producing DGLA.
|Biosynthesis of Very Long Chain Polyunsaturated Fatty Acids in Chicory|
Hattem Mekky1, Michael R. Davey1, J. Brian Power1 , Maged E. Mohamed2 and Colin M. Lazarus2
Very long chain polyunsaturated fatty acids (VLCPUFAs) are declining in reserves, since they are produced by oily fish. VLCPUFAs are important in human nutrition because they are responsible for the production of inflammatory mediators such as prostaglandins, the regulation of cholesterol synthesis and its transport, and the maintenance of cellular membranes. This research aims to produce VLCPUFAs in edible plants.
|qPCRas a primary screen in drug discovery|
GauravJaggi, Frank Boeckler, Andreas Joerger and Alan Fersht
We report the use of qPCR technique to follow the thermal unfolding of proteins by the binding of the dye SYPRO Orange, and exploit its potential as a robust and high-throughput primary screen for small molecule drug discovery.