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的技术。合适的荧光探针对于荧光成像自然是至关重要的，但由于缺乏用于荧光探针的灵活设计策略，目前只能可视化非常有限范围的生物分子。目前，设计在很大程度上是经验主义的。我们证明了作为荧光探针核心的荧光素分子可以被理解为一个直接相连的电子给体-荧光团受体系统，并且荧光素衍生物的荧光性质可以通过分子内光诱导电子转移来控制。基于这些光物理发现，我们可以构建第一个和完全合理的设计策略，为新的荧光探针。到目前为止，我们可以开发以下新型荧光探针：（a）用于单线态氧的DPAX和DMAX，（B）用于一氧化氮的DAF和DAMBO，（c）用于包括羟基自由基和过氧亚硝酸根的高活性氧物质的HPF和AIPF，等等。我们成功地开发了新的笼状化合物，其可以通过使用硝基Beuzyl部分将未笼状产物的产率报告为荧光强度的增加作为笼状保护基团和荧光素作为报告荧光团。

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)

Satoko Maruyama: "A Novel, Cell-Permeable, Fluorescent Probe for Ratiometric Imaging of Zinc Ion"J. Am. Chem. Soc.. 124. 10650-10651 (2002)

Satoko Maruyama：“一种用于锌离子比例成像的新型细胞渗透性荧光探针”J。

Tomoya Hirano: "Improved Fluorescent Probes for Zinc, ZnAFs, Suitable for Biological Applications"J. Am. Chem. Soc.. 124. 6555-6562 (2002)

Tomoya Hirano：“改进的锌、ZnAF 荧光探针，适合生物应用”J。

Ken-ichi Setsukinai: "Development of Novel Fluorescence Probes That Can Reliably Detect Reactive Oxygen Species and Distinguish Specific Species"J. Biol. Chem.. 278. 3170-3175 (2003)

Ken-ichi Settsukinai：“开发能够可靠检测活性氧并区分特定物种的新型荧光探针”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)