Yoshimura Masahiko, Sasayama Ryuto, Kajiwara Takashi, Mori Chihiro, Nakasone Yusuke, Inose Tomoko
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Institute for Advanced Study, Kyoto University, Yoshida, Sakyo-ku, Kyoto, 606-8501, Japan.
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
Angew Chem Int Ed Engl. 2025 Jun 17;64(25):e202502376. doi: 10.1002/anie.202502376. Epub 2025 Apr 25.
Photocleavable molecules are valuable tools for biological studies, enabling spatiotemporal activation of molecular functions within cellular environments. In particular, coumarin-based photolytic molecules are useful because of their ability to flexibly tune the wavelength of photostimulation through their structural modifications. Ideal photocleavable molecular tools require hydrolytic stability and selective susceptibility to photo stimuli. However, conventional coumarin-based molecules have not simultaneously achieved both highly efficient photocleavage and hydrolysis resistance. Herein, we proposed a novel molecular design concept that introduces a silyl group into coumarin-based molecules at a position remote from the photolabile bond, creating an ideal photocleavable molecule for chemical biology tools. The established orbital effect of the remotely introduced silyl group improves the photolysis efficiency of coumarin-based molecules, while its bulkiness substantially enhances their hydrolytic stability in aqueous environments and under enzymatic conditions. Furthermore, this improvement in molecular functionality contributes to the development of high-performance protein-release biomaterials.
光可裂解分子是生物学研究中的宝贵工具，能够在细胞环境中实现分子功能的时空激活。特别是，基于香豆素的光解分子很有用，因为它们能够通过结构修饰灵活调节光刺激的波长。理想的光可裂解分子工具需要水解稳定性和对光刺激的选择性敏感性。然而，传统的基于香豆素的分子尚未同时实现高效光裂解和抗水解。在此，我们提出了一种新颖的分子设计概念，即在远离光不稳定键的位置将硅烷基引入基于香豆素的分子中，从而为化学生物学工具创造出理想的光可裂解分子。远程引入的硅烷基所建立的轨道效应提高了基于香豆素的分子的光解效率，而其体积大大增强了它们在水性环境和酶促条件下的水解稳定性。此外，分子功能的这种改善有助于高性能蛋白质释放生物材料的开发。
