| Project/Area Number |
18K05359
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 37030:Chemical biology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
森岡 弘志 熊本大学, 大学院生命科学研究部(薬), 教授 (20230097)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 線維芽細胞増殖因子受容体 / チロシンキナーゼ / 二量体 / 2量体 / 阻害ペプチド / 阻害剤 / ATP結合ポケット / キナーゼドメイン間相互作用 / FGFR / 自己リン酸化 / 活性化ループ |
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| Outline of Final Research Achievements |
Receptor tyrosine kinases transiently form inter-kinase domain dimers during activation. In this study, we attempted to search for peptides that bind to the dimer interface between kinase domains of fibroblast growth factor receptor 1 (FGFR1). The helix G plays an important role in the interaction between kinase domains of FGFR1. Therefore, an interaction residue between kinase domains of helix G was introduced into one of the helices of a peptide that forms helix-loop-helix structure (HLH peptide). As a result, it was found that this peptide binds to the kinase domain of FGFR1 and enhances the auto-phosphorylation of FGFR1. The HLH peptide was prepared as a fusion protein with maltose-binding protein (MBP). It was also revealed that inexpensive corn starch can be used as an affinity chromatography carrier for the purification of the MBP fusion proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、受容体型チロシンキナーゼを活性化するペプチドを見出した。ペプチドの生産には大腸菌発現系を用いたが、ペプチド鎖長上は化学合成でも生産可能である。受容体型チロシンキナーゼを活性化するタンパク質 (成長因子・細胞増殖因子)は細胞培養の際に試薬として使用される。それらは、複雑な構造を有し、生産ロット間の品質のばらつきにつながる。今後、さらなる研究は必要だが、受容体型チロシンキナーゼを活性化するペプチドを化学合成したものが代替できれば、生産ロット間の品質格差の抑制につながる。
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