Water-Soluble BODIPY Photocages with Tunable Cellular Localization
Water-Soluble BODIPY Photocages with Tunable Cellular Localization
复制标题
DOI：
10.1021/jacs.9b13219
复制
发表时间：
2020-03-18
影响因子：
15
通讯作者：
Weinstain, Roy
中科院分区：
文献类型：
--
作者：
Kand, Dnyaneshwar;Liu, Pei;Weinstain, Roy
生物活性分子的光激活使得对细胞过程的操纵具有很高的时空精度。最近出现的可见光可激发光保护基团有可能进一步扩大光激活策略在生物应用中的既定用途，因为它提供了更高的组织穿透率，减少了光毒性，并与其他光依赖技术兼容。然而，这类应用的一个关键障碍仍然是大多数可见光可激发光笼基团的显著疏水性。在这里，我们发现，对中甲基BODIPY光笼应用传统的2，6-磺化反应与其光反应不相容，因为光释放的激发态势垒增加。我们为BODIPY光笼提供了一种简单的远程磺化解决方案，该解决方案增加了水的溶解度，并提供了对细胞渗透性的控制，同时保留了它们良好的光谱和光反应特性。外围的二磺化BODIPY光笼是细胞不渗透的，使它们有助于调节细胞表面受体，而单磺化BODIPY保留了穿过细胞膜的能力，并可以调节细胞内的靶点。这种新的方法对于控制BODIPY的定位是可推广的，并通过对哺乳动物细胞和神经元的可见光激活信号分子的敏化来验证。
Photoactivation of bioactive molecules allows manipulation of cellular processes with high spatiotemporal precision. The recent emergence of visible-light excitable photoprotecting groups has the potential to further expand the established utility of the photoactivation strategy in biological applications by offering higher tissue penetration, diminished phototoxicity, and compatibility with other light-dependent techniques. Nevertheless, a critical barrier to such applications remains the significant hydrophobicity of most visible-light excitable photocaging groups. Here, we find that applying the conventional 2,6-sulfonation to meso-methyl BODIPY photocages is incompatible with their photoreaction due to an increase in the excited state barrier for photorelease. We present a simple, remote sulfonation solution to BODIPY photocages that imparts water solubility and provides control over cellular permeability while retaining their favorable spectroscopic and photoreaction properties. Peripherally disulfonated BODIPY photocages are cell impermeable, making them useful for modulation of cell-surface receptors, while monosulfonated BODIPY retains the ability to cross the cellular membrane and can modulate intracellular targets. This new approach is generalizable for controlling BODIPY localization and was validated by sensitization of mammalian cells and neurons by visible-light photoactivation of signaling molecules.