The development of peptide tethered cNDI cluster for specifically targeting telomeric tetraplex DNA
| Project/Area Number |
19K15700
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 37010:Bio-related chemistry
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| Research Institution | Kyushu Institute of Technology |
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Principal Investigator |
ZOU TINGTING 九州工業大学, 大学院工学研究院, 特任助教 (30828637)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | G-quadruplex / naphthalene diimide / peptide linker / cluster / DNA四本鎖 / クラスター / 環状ナフタレンジイミド / ペプチドリンカー |
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| Outline of Research at the Start |
効果的な抗がん剤の開発を目指し、テロメア領域で形成可能な複数のGquadruplex（DNA四本鎖）構造を標的とする新規なG4リガンドクラスターの設計及び性能評価を行う。本提案のG4リガンドクラスターを構築するため、初めてペプチド合成ユニットのアミノ酸に環状ナフタレンジイミド（cNDI）を導入することによって、ペプチド合成装置を用いてペプチド鎖に複数のcNDIを導入する。新規cNDIクラスターは選択的にテロメア領域の複数のG-quadruplexと結合することが期待されている。
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| Outline of Final Research Achievements |
In this study, (1) we firstly employed peptide as the linker part to construct novel ligand cluster, cyclic naphthalene diimide was adopted as the base G4 ligand unit, which showed preference for G-quadruplex recognition; several pep-cNDI dimers were newly synthesized; (2) then we confirmed that pep-cNDI dimers showed enhanced preference for recognizing and stabilizing mono G-quadruplex than cNDI monomer, within the determination by CD-based Tm measurement and ITC-based binding affinity assay; (3) finally we adopted ESI-MS to analyze the binding property of pep-cNDI dimers with G-quadruplex, the results suggested that two pep-cNDI dimers prefer to bind to one G-quadruplex structure and form a much more stable complex
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| Academic Significance and Societal Importance of the Research Achievements |
We firstly adopted peptide as linker part for constructing G4 ligand cluster, and confirmed the high potentiality of peptide as linker, which could enrich the development of new group of G4 ligands.
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Report
(3 results)
Research Products
(12 results)
