Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260-3000, United States.
J Am Chem Soc. 2022 Jan 12;144(1):57-62. doi: 10.1021/jacs.1c10354. Epub 2021 Dec 29.
Here we report the design of a superfast bioorthogonal ligation reactant pair comprising a sterically shielded, sulfonated tetrazole and bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN). The design involves placing a pair of water-soluble -sulfonylpyrrole substituents at the C-phenyl ring of diphenyltetrazoles to favor the photoinduced cycloaddition reaction over the competing nucleophilic additions. First-principles computations provide vital insights into the origin of the tetrazole-BCN cycloaddition's superior kinetics compared to the tetrazole-spirohexene cycloaddition. The tetrazole-BCN cycloaddition also enabled rapid bioorthogonal labeling of glucagon receptors on live cells in as little as 15 s.
在这里，我们报告了一种超快生物正交连接反应试剂对的设计，该试剂对由一个空间位阻保护的、磺酸化的四唑和双环[6.1.0]壬-4-炔-9-基甲醇（BCN）组成。该设计涉及在二苯四唑的 C-苯基环上放置一对水溶性 -磺酰基吡咯取代基，以有利于光诱导环加成反应而不是竞争的亲核加成。第一性原理计算为四唑-BCN 环加成的动力学优于四唑-螺环己烯的环加成提供了重要的见解。四唑-BCN 环加成还能够在短短 15 秒内快速对活细胞上的胰高血糖素受体进行生物正交标记。
