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Research paper : A systematic analysis of protein interaction networks leading to the drug discovery (S. Iemura et al.)−115 Synthesiology - English edition Vol.1 No.2 (2008) peptides are adsorbed and concentrated in the column carrier from the initial solvent. After desalt, elution solvent is discarded and the eluted sample is analyzed. Normally, the elution solvent is mixed gradually with initial solvent, and the liquid is delivered by generating a concentration gradient. To accomplish this, flow path for mixed delivery is necessary by connecting the pumps of two systems for initial and elution solvents. Check valve and dead volume of mixer (space to thoroughly mix the solvents) are always present in the flow path. Therefore, single analysis takes a long time, and solvents cannot be mixed evenly at a slow flow rate. In the 1990s, much research was done to decrease the flow rate by splitting the liquid delivery without slowing down the flow speed of the pump. A branch was formed in the flow path, most of the solvent was discarded, and part of the solvent was sent to the analytical column. If the split was 10 against 1, 9 parts of the solvent could be discarded and the flow rate was reduced to 1/10 (upper part of Figure 2). In this method, it was not possible to conduct analysis at a set flow rate unless the backpressure of analytical column and resistance at the split part were always constant. However, in actual practice, the backpressure of analytical column was not necessarily constant depending on load and volume of the sample. Also, the split resistance tended to increase as the frequency of analysis increased. Therefore, it was almost impossible to conduct reproducible microanalysis. This was an issue that must be definitely solved.3 New scenario and development of elemental technology (issue of LC environment)The scenario we employed to solve this issue was based on increasing the performance of LC. The first task was to increase the performance of LC, and then individual elemental issues would be solved as they arose, and finally we could achieve efficient high-precision protein analysis.To increase performance of LC, we created a totally new method in which a single-system pump was used instead of a dual-system to generate concentration gradient in the elution solvent. By using a single-system pump, the flow channel could be dramatically simplified, and the dead volume, which was the greatest challenge of LC at low flow, could be minimized. Also, if this were realized, low speed liquid transfer would be possible without splitting. Here, we devised the novel split-less nano-flow gradient elution system. The system consists of several channel solvent reservoirs connected by a ten-port electrical switching valve and a manifold. Each reservoir was filled with step elution solvent for LC, which was supplied from two separate reservoirs for initial and final solvents by an Fig. 1 Drug discovery from protein network analysis.Proteins interact with each other and form networks. By understanding the protein network, we can discern the function of individual protein. Also, by overlooking these networks, we can find pathogenic mechanisms and new drug discovery targets. Drug discovery screening is conducted based on these informations.(43)−Analysis of disease-related protein networkCompound libraryBy overlooking the protein network, optimal control molecules (drug discovery targets) that were previously hidden can be foundConstruction of screening systemSynthesisImprovements of throughput and accuracy throughauto-processing robotLarge-scale protein network analysisClarification of functions of disease-related genes・Life style disease・Essential hypertension・Neurodegenerative disease・Cancer・Rheumatism・Disuse muscle atrophy・Down syndrome・Xeroderma pigmentosum・Behcet’s diseaseAccelerateddrug discoveryDiscovery of a new cellular systemDiscovery of a new cellular systemOptimization within silico supportRobot synthesis technologyAIST super clusterBlue GeneA1~A10C1~C10B1~B10D1~D1010×10×10×10=10,000

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