Development of novel caged compounds that can report the yield of uncaged products

开发新型笼状化合物，可以报告非笼状产物的产率

• 批准号: 13557209
• 负责人: URANO Yasuteru
• 金额: $ 8.96万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557209/
• 关键词: Fluorescein; Caged compounds; Photoinduced Electron Tranfer; Nitrobenzyl group; 7 -Hydroxycoumarin; Marcus theory; Confocal fluorescence microscope; Photo-functional molecule; o-Nitrobenzyl基; 計算化学; 電荷分離状態; レーザーフラッシュフォトリシス; o-nitrobenzyl基

Fluorescence imaging is the most powerful technique currently available for continuous observation of dynamic intracellular processes in living cells. Suitable fluorescence probes are naturally of critical importance for fluorescence imaging, but only a very limited range of biomolecules can currently be visualized because of the lack of flexible design strategies for fluorescence probes. At present, design is largely empirical. We demonstrated here that the fluorescein molecule, which has been widely employed as a core of fluorescence probes, could be understood as a directly linked electron donor -fluorophore acceptor system and that the fluorescence properties of fluorescein derivatives could be controlled by intramolecular photoinduced electron tranfer. Based on these photo-physical findings, we could construct the first and totally rational design strategy for novel fluorescence probes. We could develop so far the following novel fluorescence probes; (a) DPAXs and DMAXs for singlet oxygen, (b) DAFs and DAMBOs for nitric oxide, (c) HPF and AIPF for highly reactive oxygen species including hydroxyl radical and peroxynitrite, and so on. Further, we succeeded in developing novel caged compounds that can report the yield of uncaged products as an increase of fluorescence intensity by employing a nitrobeuzyl moiety as a caging protective group and fluorescein as a reporting fluorophore.

荧光成像是目前可用于连续观察活细胞中动态细胞内过程的最强大技术。合适的荧光探针自然对于荧光成像至关重要，但是由于缺乏用于荧光探针的柔性设计策略，目前只能可视化非常有限的生物分子范围。目前，设计在很大程度上是经验的。我们在这里证明，已广泛用作荧光探针的核心的荧光素分子可以理解为直接连接的电子供体 - 荧光团受体系统，并且荧光素衍生物的荧光特性可以由内部分子光诱导的电子诱导的电子tranfer控制。基于这些光物理发现，我们可以为新型荧光探针构建第一个且完全合理的设计策略。我们可以开发以下新的荧光探针。 （a）用于单线氧的DPAX和DMAXS，（b）DAFS和DAMBOS用于一氧化氮，（C）HPF和AIPF，用于高活性氧，包括羟基自由基和过氧亚硝酸盐，等等。此外，我们成功地开发了新型的笼中化合物，这些化合物可以通过使用硝基烷基部分作为笼子保护组和荧光素作为报告荧光团来报告未分泌产物的产量，以增加荧光强度的增加。

项目成果

Yu Gabe: "Highly Sensitive Fluorescence Probes for Nitric Oxide Based on Boron Dipyrromethene Chromophore. -Rational Design of Potentially Useful Bioimaging Fluorescence Probe-"J.Am.Chem.Soc.. 126. 3357-3367 (2004)

Yu Gabe：“基于硼二吡咯亚甲基发色团的一氧化氮高灵敏荧光探针。-潜在有用的生物成像荧光探针的合理设计-”J.Am.Chem.Soc.. 126. 3357-3367 (2004)

Yu Gabe, Yasuteru Urano, Kazuya Kikuchi, Hirotatsu Kojima, Tetsuo Nagano: "Highly Sensitive Fluorescence Probes for Nitric Oxide Based on Boron Dipyrromethene Chromophore. -Rational Design of Fluorescence Probe-"J. Am. Chem. Soc.. 126. 3357-3367 (2004)

Yu Gabe、Yasuteru Urano、Kazuya Kikuchi、Hirotatsu Kojima、Tetsuo Nagano：“基于硼二吡咯亚甲基发色团的一氧化氮高灵敏荧光探针。-荧光探针的合理设计-”J。

Kumi Tanaka: "Rational Design of Fluorescein-based Fluorescence Probes. -Mechanism-based Design of a Maximum Fluorescence Probe for Singlet Oxygen-"J.Am.Chem.Soc.. 123. 2530-2536 (2001)

Kumi Tanaka：“基于荧光素的荧光探针的合理设计。-单线态氧最大荧光探针的基于机制的设计-”J.Am.Chem.Soc.. 123. 2530-2536 (2001)

Noriyuki Suzuki: "Orthogonality of Calcium Concentration and Ability of 4,5-Diaminofluorescein (DAF-2) to Detect NO"J.Biol.Chem.. 277. 47-49 (2002)

Noriyuki Suzuki：“钙浓度的正交性和 4,5-二氨基荧光素 (DAF-2) 检测 NO 的能力”J.Biol.Chem.. 277. 47-49 (2002)

Noriyuki Suzuki: "Orthogonality of Calcium Concentration and Ability of 4, 5-Diaminofluorescein(DAF-2)to Detect NO"J.Bjol.Chem.. 277. 47-49 (2002)

Noriyuki Suzuki：“钙浓度的正交性和 4, 5-二氨基荧光素 (DAF-2) 检测 NO 的能力”J.Bjol.Chem.. 277. 47-49 (2002)