2021 Fiscal Year Final Research Report
Caged compounds for NO and its related signaling molecules with multimodal control, and their biological applications
Project/Area Number |
19H03354
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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Research Institution | Nagoya City University |
Principal Investigator |
Nakagawa Hidehiko 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (80281674)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | ケージド化合物 / 一酸化窒素 / 近赤外光 / 血管弛緩 |
Outline of Final Research Achievements |
Based on our previous findings, we performed the research aiming at the red and near-infrared control of caged NO, and developed caged NO with photoinduced electron transfer (PeT) mechanism as the key reaction. By substituting the dye moiety for using various wavelengths of light, we showed that NO was released in response to light in the red and near-infrared region around 600 nm and 650 nm. Furthermore, we demonstrated that light irradiation induced the vasorelaxation effect by the Magnus test using rat aorta specimen, and we verified the blood pressure change by light irradiation through the in vivo rat vasorelaxation experiment, so that the local blood pressure was succeeded to be controlled without affecting the systemic blood pressure. In addition, we also demonstrated NO release using organic dyes for nanoparticle-type caged NO.
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Free Research Field |
創薬化学・ケミカルバイオロジー
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Academic Significance and Societal Importance of the Research Achievements |
NOとその関連活性種は短寿命シグナル分子であり実験的取り扱いが困難であるため研究には供与剤が用いられる。光で投与制御が可能な供与剤であるケージド化合物は、短寿命シグナル分子の詳細な生理機能を解析する上で有用であり、治療研究への応用も期待される。さらに、疾患の治療研究等in vivo実験に利用するには生体透過性の高い光で制御できる必要がある。 本研究で開発した赤色-近赤外光ケージドNOは、ex vivo系およびin vivo系でNOの生理機能の1つである血管拡張作用の光制御が可能であることが示され、局所で作用する副作用の少ない薬剤・治療法開発に発展することが期待される。
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