Development of functional human serum albumin (HSA) mutants and studies of their ABT recognition mechanisms
| Project/Area Number |
24390028
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
MORIOKA HIROSHI 熊本大学, 大学院生命科学研究部(薬学系), 教授 (20230097)
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| Co-Investigator(Kenkyū-buntansha) |
OTAGIRI Masaki 崇城大学, 薬学部, 教授 (80120145)
KOBASHIGAWA Yoshihiro 熊本大学, 大学院生命科学研究部, 准教授 (90455600)
SUWA Yoshiaki 熊本大学, 薬学部, 特任助教 (50516127)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2013: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2012: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
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| Keywords | 薬物認識 / ヒト血清アルブミン / ビリルビン / タンパク質工学 / 分子進化工学 / ファージディスプレイ / ランダム変異 / ビリルビン排泄促進剤 |
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| Outline of Final Research Achievements |
We have obtained several recombinant human serum albumin (HSA) domain II mutant proteins with high bilirubin (BR) binding affinity by phage display technology. The BR binding affinity of RWLR mutant was found to be 7 times higher than that of WT (FWRR). The results of docking simulation studies and induced CD spectra analyses of BR bound to HSA domain II protein (WT and RWLR mutant) showed that the entrance of BR-binding pocket in RWLR mutant has expanded by the replacement of Arg with Leu at position 218, suggesting that BR could enter the binding pocket more deeply as compared with WT (FWRR). Administration of RWLR mutant reduced serum BR level and increased its urinary excretion in the disease model mice as compared to WT (FWRR) treatment.
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Report
(4 results)
Research Products
(8 results)
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[Book] Advanced Methods in Structural Biology (Surface Plasmon Resonance)2015
Author(s)
Kobashigawa, Y., Fukuda, N., Nakahara, Y., Morioka, H. (Senda, T. and Maenaka, K., eds)
Total Pages
15
Publisher
Springer
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