National Centre of Competence in Research (NCCR) Chemical Biology, School of Chemistry and Biochemistry, University of Geneva, CH-1211, Geneva, Switzerland.
National Centre of Competence in Research (NCCR) Molecular Systems Engineering, CH-4002, Basel, Switzerland.
Chemistry. 2019 Mar 15;25(16):4047-4051. doi: 10.1002/chem.201805900. Epub 2019 Feb 28.
Cyclic oligochalcogenides are emerging as powerful tools to penetrate cells. With disulfide ring tension maximized, selenium chemistry had to be explored next to enhance speed and selectivity of dynamic covalent exchange on the way into the cytosol. We show that diseleno lipoic acid (DiSeL) delivers a variety of relevant substrates. DiSeL-driven uptake of artificial metalloenzymes enables bioorthogonal fluorophore uncaging within cells. Binding of a bicyclic peptide, phalloidin, to actin fibers evinces targeted delivery to the cytosol. Automated tracking of diffusive compared to directed motility and immobility localizes 79 % of protein-coated quantum dots (QDs) in the cytosol, with little endosomal capture (0.06 %). These results suggest that diselenolanes might act as molecular walkers along disulfide tracks in locally denatured membrane proteins, surrounded by adaptive micellar membrane defects. Miniscule and versatile, DiSeL tags are also readily available, stable, soluble, and non-toxic.
环多硫化物作为穿透细胞的有力工具正在兴起。为了提高进入细胞质时动态共价交换的速度和选择性，必须探索二硫键张力最大化的硒化学。我们表明，二硒辛酸（DiSeL）可以输送多种相关底物。DiSeL 驱动的人工金属酶摄取使细胞内的生物正交荧光团去笼成为可能。双环肽鬼笔环肽与肌动蛋白纤维的结合表明靶向递送至细胞质。与定向运动和非运动相比，扩散的自动跟踪将 79%的涂有蛋白质的量子点 (QD) 定位在细胞质中，内体捕获很少 (0.06%)。这些结果表明，二硒烷可能作为分子步行者沿着局部变性膜蛋白中的二硫键轨道移动，周围是适应性胶束膜缺陷。微小而多功能的 DiSeL 标签也很容易获得，稳定、可溶且无毒。
