Development of novel cyclic peptides that detect molecular states of collagen in vitro and in vivo
| Project/Area Number |
17K19502
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmaceutical Sciences and related fields
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| Research Institution | Waseda University |
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Principal Investigator |
KOIDE Takaki 早稲田大学, 理工学術院, 教授 (70322253)
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| Co-Investigator(Kenkyū-buntansha) |
木村 寛之 京都薬科大学, 薬学部, 准教授 (50437240)
増田 亮 早稲田大学, 理工学術院, 次席研究員(研究院講師) (90632159)
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| Research Collaborator |
TAKITA Koh K.
FUJII Kazunori K.
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | コラーゲン / ペプチド / イメージング / 薬物送達 / がん / 3重らせん |
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| Outline of Final Research Achievements |
It is proposed that tissues surrounding malignant tumors are rich in (partially) denatured collagen. Thus, development of a probe that detects denatured collagen with high efficiency has been expected. In this study, based on the design of previously published peptides capable of hybridizing with an unfolded triple helix, we have developed peptides that can detect it with higher sensitivity. The peptides are cyclic dimers of peptides with collagen-like sequences. One of the cyclic peptides showed two-orders of magnitude higher affinity to denatured collagen than conventional single chain counterpart. The peptide was shown to be applicable to sensitive detection of collagen in vitro. In addition, it enabled in vivo fluorescent imaging of malignant tumors in mouse models.
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| Academic Significance and Societal Importance of the Research Achievements |
がん、骨・軟骨疾患、線維化、炎症性疾患などでコラーゲン３重らせんが変性していることが予想されており、それを検出するプローブの開発が求められていた。これまでに１本鎖のコラーゲン様ペプチドがこの目的で試されてきたが、本研究においては、分子設計の改変により約２オーダーの結合能の改善を達成できた。これにより、培養細胞レベルから生体のイメージングに至る広範囲な実験系において、緩んだ３重らせんを検出、定量、可視化することが可能となった。この成果は、基礎研究から診断薬・治療薬開発を目指した応用研究まで幅広い研究領域にひとつの新たなツールを付け加えた。
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Report
(3 results)
Research Products
(10 results)
