Studies on new chemical probes development that assumed dimeric interface of the EGF receptor ectodomain a target
| Project/Area Number |
26893061
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Drug development chemistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Mizuguchi Takaaki 東京医科歯科大学, 生体材料工学研究所, 助教 (30732557)
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| Co-Investigator(Renkei-kenkyūsha) |
TAMAMURA Hirokazu 東京医科歯科大学, 生体材料工学研究所, 教授 (80217182)
NOMURA Wataru 東京医科歯科大学, 生体材料工学研究所, 准教授 (80463909)
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| Research Collaborator |
AKAJI Kenichi 京都薬科大学, 薬学部, 教授 (60142296)
TOYAMA Kei 東京医科歯科大学, 大学院医歯学総合研究科, 大学院生
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | EGFレセプター / 二量化阻害 / 二量体化アーム / 蛍光プローブ / 抗がん活性ペプチド / 細胞内薬物送達分子 / 環状ペプチド / フルオレセイン / フルオレセイン標識 / 細胞内輸送 / 抗がん薬リード / 共焦点レーザー顕微鏡 / ＥＧＦレセプター / アラニン置換 / 抗がん薬 / 創薬研究 / 二量化アーム |
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| Outline of Final Research Achievements |
We have developed a cyclic decapeptide 1, which acts on the extracellular region of the EGF receptor, preventing it from dimerizing. Fluorescein-labeled peptide 2 at the N-terminus of peptide 1 was synthesized. Peptide 2 essentially retained the inhibitory activity of peptide 1 against the receptor autophosphorylation. Confocal microscopy studies revealed that in carcinoma cells, the fluorescence of peptide 2 was localized inside some vesicles. Treatment of intact cells by peptide 1 in combination with peptide 2 decreased the fluorescence intensity significantly compared to treatment with only peptide 2. Seven derivatives of peptide 2 were synthesized and used to treat the cells. Peptides 6 and 9 showed the highest fluorescence intensity in cells. These two derivatives were proven to have higher inhibitory activity against the autophosphorylation than peptide 2, which would therefore be a useful delivery peptide and fluorescent probe to find new inhibitors against the EGF receptor.
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Report
(3 results)
Research Products
(13 results)
