Ligand discovery based on biophysical analyses
| Project/Area Number |
25249115
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biofunction/Bioprocess
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Tsumoto Kouhei 東京大学, 工学(系)研究科(研究院), 教授 (90271866)
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| Co-Investigator(Kenkyū-buntansha) |
NAGATOISHI Satoru 東京大学, 大学院工学系研究科, 助教 (30550248)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥41,210,000 (Direct Cost: ¥31,700,000、Indirect Cost: ¥9,510,000)
Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2013: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
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| Keywords | 低分子創薬 / 熱力学解析 / フラグメントスクリーニング / 相互作用 / 蛋白質 / 低分子スクリーニング / 熱力学 / 生物・生体工学 / 分子認識 / 物理化学 |
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| Outline of Final Research Achievements |
We studied fragment-based drug discovery based on the biophysical methods, including isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and differential scanning calorimetry (DSC). The hit compounds bound specifically to target proteins; the interactions between compounds and the targets were validated using these biophysical measurements and the binding mechanisms have been characterized thermodynamically. We carried out X-ray crystallographic analyses and in silico docking simulation to discuss the thermodynamics of the interactions. The crystal structure and docking simulation supported thermodynamic data. Moreover, one hit compound was optimized to bind strongly to the target protein, of which dissociation constant showed sub-micro molar. This research provides a novel rational strategy to obtain the true-hit compounds through screening small molecule compounds.
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Report
(4 results)
Research Products
(81 results)
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[Journal Article] Epiregulin Recognition Mechanisms by Anti-epiregulin Antibody 9E5: STRUCTURAL, FUNCTIONAL, AND MOLECULAR DYNAMICS SIMULATION ANALYSES.2016
Author(s)
Kado Y1, Mizohata E2, Nagatoishi S3, Iijima M4, Shinoda K4, Miyafusa T3, Nakayama T2, Yoshizumi T2, Sugiyama A4, Kawamura T4, Lee YH4, Matsumura H2, Doi H4, Fujitani H4, Kodama T4, Shibasaki Y4, Tsumoto K5, Inoue T6.
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Journal Title
J Biol Chem.
Volume: 291
Issue: 5
Pages: 2319-2330
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Structural and thermodynamics basis of epitope binding to neutralizing and non-neutralizing forms of the anti-HIV-1 4E10 antibody2015
Author(s)
Rujas, E., Gulzar, N., Morante, K., Tsumoto, K., Scott, J.K., Nieva, J.L. and Caaveiro, J.M.M.
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Journal Title
Journal of Virology
Volume: 89
Issue: 23
Pages: 11975-11991
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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