Ultra-sensitive cancer diagnosis based on cyclic ferrocenylnaphthalene diimide
| Project/Area Number |
19H02748
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 34020:Analytical chemistry-related
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| Research Institution | Kyushu Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | フェロセン化ナフタレンジイミド / 環状ナフタレンジイミド / テロメラーゼ / 電気化学的検出 / DNAチップ / 4本鎖DNA / テロメアDNA / がん診断 / 電気化学 / 電気化学検出 |
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| Outline of Research at the Start |
がんの早期診断法の確立を目指して、電気化学的テロメラーゼアッセイ法に最適なプローブ分子として環状フェロセン化ナフタレンジイミド(cFND)を開発する。テロメラーゼは、がんのマーカーとして期待されており、テロメラーゼの基質DNAであるTSプライマーを電極に固定化したセンサチップにテロメラーゼを作用させるとTSプライマーが伸長される。これを電気化学シグナルへ変換し、間接的にテロメラーゼ活性を検出する。この変換で用いるcFNDは、単独電解液中ではフェロセンの酸化電流が抑えられ、テロメラーゼで伸長されたテロメアDNAが形成する4本鎖DNAに結合した際に酸化電流が生ずるシグナルオン型検出系を構築する。
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| Outline of Final Research Achievements |
Telomerase is a promising marker for cancer. An electrochemical telomerase assay (ECTA) using ferrocenylnaphthalene diimides has been developed. We have previously been developing the strong binder for G-quartet DNA using novel type of cyclic naphthalenediimide. Therefore, cyclic ferrocenylnaphthalene diimides (cFNDs) 1 and 2 were developed as indicators for ECTA. cFNDs by themselves suppress the current due to the interaction of ferrocene and naphthalene diimide parts, and their binding to G-quadruplex DNA are expected to recover their expressed current. Both 1 and 2 strongly interact with TA-core, as shown derived from ITC and Tm measurements. cFND solutions were used to measure the SWV of G-quartet and single-stranded DNA-immobilized electrodes. The results showed that 2 exhibited high G-quadrupex selectivity. Finally, ECTA using 2 showed the current increase of 86% in the presence of telomerase of sample.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでにフェロセン化ナフタレンジイミドによるECTAでは臨床サンプルで高精度ながんの診断を確立してきた。しかし、前がん病変の応答はがんと健常者の間に位置していた。前がんをより高精度に検出できれば、がんの超早期診断につながり、また本手法によるがんの予後診断にも利用できると思われる。がんの診断は、内視鏡検査、CTなど患者の負担の大きな検査が多い。これに代わる簡便な定量的診断方法の確立は、再発を含めたがんの早期診断につながり、患者のQOLの向上および医療費削減につながるものである。
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.2021
Author(s)
Fukuda, H., Sato, S., Zou, T., Higashi, S., Takahashi, O., Habu, M., Sasaguri, M., Tominaga, K., Takenaka, S., Takeuchi, H.
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Journal Title
Bioorg. Med. Chem. Lett.
Volume: 50
Pages: 128323-128323
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chemical Modulation of DNA Replication along G-Quadruplex Based on Topology-Dependent Ligand Binding2021
Author(s)
S. Takahashi, A. Kotar, H. Tateishi-Karimata, S. Bhowmik, Z.-F. Wang, T.-C. Chang, S, Sato, S. Takenaka, J. Plavec, and N. Sugimoto
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Journal Title
J. Am. Chem. Soc.
Volume: 143
Issue: 40
Pages: 16458-16469
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Electrochemical sensory detection of: Sus scrofa mtDNA for food adulteration using hybrid ferrocenylnaphthalene diimide intercalator as a hybridization indicator2020
Author(s)
Norzila Kusnin, Nor Azah Yusof, Jaafar Abdullah, Suriana Sabri, Faruq Mohammad, Shuhaimi Mustafa, Nurul Asyikeen Ab Mutalib, Shinobu Sato, Shigeori Takenaka, Nor Azizah Parmin, Hamad A. Al-Lohedan
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Journal Title
RSC Advances
Volume: 46
Issue: 46
Pages: 27336-27336
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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