Development of fluorescent probes with AND-logic gate response for HYPOXIA
| Project/Area Number |
19K23816
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0801:Pharmaceutical sciences and related fields
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| Research Institution | Kobe Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アンドロジック / 蛍光プローブ / 微量元素 / シグナル増強 / 低酸素環境 / がん微小環境 / AＮＤロジック / ドラッグデリバリー / ANDロジックゲート / Fluorescent probe / HYPOXIA / AND logic gate / Enzyme prodrug / Cancer therapy |
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| Outline of Research at the Start |
HYPOXIAは一時的な虚血状態(梗塞や創傷)や腫瘍深部で発生し、心筋梗塞や腫瘍の治療における重要な標的イベントである。そこでHYPOXIAを検出する分子プローブはこれら疾患の解析や治療で有用と思われるが、従来の分子設計では疎水性が高く肝臓などへの非特異吸着が問題であった。そこで本研究では、細胞内の還元的環境を標的とした従来の分子設計に加えて、HYPOXIAで発現増強している細胞表面マーカーを標的とした親水性の高い分子設計を組み合わせて、高い選択性でHYPOXIAを検出可能なANDロジックゲート型のプローブ分子を開発することを目指す。
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| Outline of Final Research Achievements |
Our research goal is the development of an AND logic gate targeting tumor-localized enzymes with a conventional hypoxia-sensitive molecule. In this project, we found that the enzyme we had planned to use for this system quickly degrades under physiological conditions, but a chemical modification of the enzyme overcame this issue. In addition, the enzyme substrate was also found to be unstable under physiological conditions, and the structure optimization efforts is underway. Through these optimization studies, we fortuitously found functional molecules that react selectively with zinc. The molecules were further applied as fluorescent probes to give a bright fluorescent response by signal amplification. These studies are also in progress and a part of results has been published in an international journal.
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| Academic Significance and Societal Importance of the Research Achievements |
研究に用いる酵素の安定性を増す化学修飾方法を開発することでケミカルバイオロジー研究での新たなツールとなることが期待される。また本研究では、偶然に亜鉛に対するシグナル増強型の蛍光プローブを創製した。従来のプローブ分子に比べて高感度であり、生体中での微量の亜鉛を蛍光解析するのに優れた機能を持つ。また本研究概念は他の微量元素や生体内分子の検出に拡張可能であると思われ、蛍光プローブの開発における新たな分子設計指針としても有効であることが期待される。
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Non-genetic cell-surface modification with a self-assembling molecular glue2021
Author(s)
Hakariya, H., Takashima, I., Takemoto, M., Noda, N., Sato, S., Uesugi, M.
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Journal Title
Chem Commun.
Volume: 57
Issue: 12
Pages: 1470-1473
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Discovery of Self‐Assembling Small Molecules as Vaccine Adjuvants2020
Author(s)
Jin Shuyu、Vu Hue Thi、Hioki Kou、Noda Naotaka、Yoshida Hiroki、Shimane Toru、Ishizuka Shigenari、Takashima Ippei、Mizuhata Yoshiyuki、Beverly Pe Kathleen、Ogawa Tetsuya、Nishimura Naoya、Packwood Daniel、Tokitoh Norihiro、Kurata Hiroki、Yamasaki Sho、Ishii Ken J.、Uesugi Motonari
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Journal Title
Angewandte Chemie International Edition
Volume: 60
Issue: 2
Pages: 961-969
DOI
NAID
Related Report
Peer Reviewed / Int'l Joint Research
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