Department of Organic Chemistry, National Centre of Competence in Research (NCCR) Chemical Biology, University of Geneva, Geneva, Switzerland.
Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202113163. doi: 10.1002/anie.202113163. Epub 2021 Nov 23.
Mechanosensitive flipper probes are attracting interest as fluorescent reporters of membrane order and tension in biological systems. We introduce PhotoFlippers, which contain a photocleavable linker and an ultralong tether between mechanophore and various targeting motifs. Upon irradiation, the original probe is released and labels the most ordered membrane that is accessible by intermembrane transfer. Spatiotemporal control from photocleavable flippers is essential to access open, dynamic or elusive membrane motifs without chemical or physical interference. For instance, fast release with light is shown to place the original small-molecule probes into the innermost leaflet of the nuclear envelope to image changes in membrane tension, at specific points in time of membrane trafficking along the secretory pathway, or in the inner leaflet of the plasma membrane to explore membrane asymmetry. These results identify PhotoFlippers as useful chemistry tools to enable research in biology.
机械敏感的 flipper 探针作为生物系统中膜有序性和张力的荧光报告子引起了人们的兴趣。我们引入了 PhotoFlippers，它在机械敏感元件和各种靶向结构域之间包含一个光可裂解的连接子和一个超长的连接臂。在照射下，原始探针被释放，并标记可通过膜间转移到达的最有序的膜。光可裂解 flipper 的时空控制对于在不进行化学或物理干扰的情况下，接近开放、动态或难以捉摸的膜结构域是至关重要的。例如，用光快速释放表明，将原始的小分子探针置于核膜的最内层小叶中，以在特定的时间点对膜张力的变化进行成像，在沿着分泌途径的膜运输过程中的特定时间点，或者在质膜的内小叶中，以探索膜不对称性。这些结果表明，PhotoFlippers 是一种有用的化学工具，可用于生物学研究。
