|Efficient discovery and optimization using high-throughput experimentation and Predictive Design Technology™|
James N. Cawse
The new emphasis of high throughput experimentation is the discovery of “hits” by searching extensive experimental spaces. These have the issues of: • High-dimensions; • Synergies (nonlinear interactions) ; • Unpredictable behavior. ProtoLife Srl has developed Predictive Design Technology™ (PDT™) to deal with these issues using proprietary algorithms. It been successfully tested in complex experimental spaces involving drugs, catalysts, and formulations.
|Lead Optimization Computational Protocol at PDB Scale to Rationally Optimize Attachments to a Given Kinase Inhibitor Scaffold|
Moriaud F., Henry T., Adcock S.A., Vorotynsev A.M., Martin L., Doppelt O.
We’ve used MED-SuMo to query and mine the Protein’s Surface Chemical Functions surrounding fragments of PDB ligands, seeking similarities with the kinase of interest (Vegfr DFGout, pdb code 2oh4, ligand code GIG) and collecting a library of 1129 unique fragments positioned in the vegfr’s active site and annotated with the counts of contacts and h-bonds. With them we optimize a substructure of the GIG ligand to find others DFGout ligands.
|Tackling the Problem of Hit Rate Enrichment by Virtual Screening: Quality-Driven Bioactive Conformations and Pharmacophore-Biased Creative Search|
Nasonov, Anatoliy F., Pletnev Igor V.
Novel ChemoSoft(TM) software tools addressing the problem of generation of bioactive conformations and virtual screening hit rate enrichment have been created.
|A new exposure system for the in vitro detection of GHz field effects on neuronal networks|
Philipp J. Koester, Jan Sakowski, Werner Baumann, Hans-Walter Glocka, Jan Gimsa
Different ideas exist about possible targets for biological effects of electromagnetic fields (EMF). One of the favourite systems are the membranes of nerve cells, e.g. in the central nervous system. Our aim is to clarify whether EMF exposure may induce athermal effects. In the experiments, direct electrophysiological in vitro measurements are conducted on neuronal networks exposed to EMF, i.e. possible changes in the action potential patterns produced by the networks are detected. The technique
|High Throughput In-silico Screening with flexible receptors|
Horacio Emilio P´erez S´anchez, Bernhard Fischer, Holger Merlitz and Wolfgang Wenzel
For thymidine kinase (TK), 10 substrates are known along with their docked X-ray structures. The corresponding binding pockets differ among each other in their orientations of certain side-chains. We report attempts to include side-chain flexibility to our docking tool FlexScreen while screening the substrates against a database of 10000 ligands.
|Microwave-Assisted Rapid Access to Bio-active Heterocycles |
Vivek Polshettiwar and Rajender S. Varma
Environmentally benign protocols have been developed for the synthesis of various pharmaceutically active heterocycles namely 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 1,3-dioxanes, pyrazoles, hydrazones and 3,4-dihydropyrimidin-2(1H)-ones, which proceed under the influence of microwave irradiation and using eco-friendly conditions. These greener protocols were catalyzed efficiently by solid supported Nafion®NR50, phosphorus pentasulfide on alumina under solvent-free conditions.
|Caveolin-1 Expression as a Possible Biomarker in Pancreatic Cancer Diagnosis|
C. Tanase, E. Raducan, L. Albulescu, E. Codorean, M.I. Nicolescu, D.I. Popescu, M.L. Cruceru and A.C. Popa
Caveolin1 (Cav-1) function either as a tumor supressor or as a promoter of metastasis. Overexpresion of cav-1 was correlated with: tumoral grading, proliferration markers (Ki67, p53), serum tumor markers (CEA, CA19.9) and angiogenic markers (VEGF, bFGF).
|New Accessories for High Throughput and Combinatorial Approach in a Microwave Batch Reactor|
Alexander Stadler, Thomas Karner, Matthias Treu
A unique sealable well-plate system is introduced allowing screening reactions in a 8x6 well format with operation limits of 200°C and 20 bar and a reaction volume of 0.3 mL per well. An appropriate turntable enables to proceed up to 4 of these SiC well plates in one run resulting in 192 parallel reactions at a time. Reaction control is achieved by sensing the IR temperature of the plate surface.
|Facile Synthesis of Hydrocarbon-Stapled Peptides|
Wei Qiu, Ling Sheng, Peng Zou, Ke Yang, Anita Hong and Xiaohe Tong
This poster describes a versatile synthesis method for hydrocarbon-stapled peptides. Asymmetric synthesis of (S)-Fmoc-a-(2’-pentenyl)-alanine was successfully accomplished via an Ala-Ni (II)-BPB-complex  in three steps with a 40% total yield. The 12-mer peptide containing two a- pentenyl-alanines on positions 4 and 8 was synthesized by Fmoc solid phase synthesis method. After olefin metathesis and cleavage, the peptide was purified by HPLC to obtain the hydrocarbon-stapled peptide.