Yan Weitao, Liu Wenchao, Zhang Qinshuo, Lin Wentao, Liao Yujie, Geng Yiqun, Wang Ruo, Xu Chunfa
Key Laboratory of Molecular Synthesis and Functionalization Discovery, College of Chemistry, Fuzhou University, Fuzhou, 350108, China.
State Key of Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Media, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
ACS Cent Sci. 2025 Jul 7;11(8):1400-1407. doi: 10.1021/acscentsci.5c00650. eCollection 2025 Aug 27.
Glycosylseleno scaffolds exhibit wide-ranging applications in multidisciplinary fields, particularly in drug discovery and biophysical chemistry, where they serve as valuable tools for biomolecular structural analysis. However, efficient methods toward glycosylseleno scaffolds remain underexplored. Herein, we present the design of a novel class of bench-stable reagents, glycosylseleno-sulfonates, which uniquely integrate radical reactivity with electrophilic properties, thereby facilitating the straightforward incorporation of glycosylseleno moieties under mild reaction conditions. Upon photoirradiation, the radical addition of alkynes with glycosylseleno-sulfonates proceeds at an exceptionally fast rate, achieving completion in less than 1 min. Likewise, the functionalization of cysteine-containing molecules is achieved in a comparably short time frame, typically within 1 min in most instances. Additive experiments involving various amino acids confirm the robustness of these transformations, demonstrating consistently high efficiency across diverse reaction environments with negligible interference. Importantly, successful peptide and protein labeling in aqueous conditions highlights the method's potential for bioorthogonal applications. These findings collectively underscore the broad applicability and operational simplicity of glycosylseleno-sulfonates in developing rapid and efficient labeling techniques for biological and chemical research. This work not only advances synthetic methodologies for glycosylseleno scaffolds but also opens new avenues for functional studies of complex biological systems.
糖基硒支架在多学科领域有着广泛的应用，尤其是在药物发现和生物物理化学方面，它们是生物分子结构分析的宝贵工具。然而，针对糖基硒支架的有效方法仍未得到充分探索。在此，我们展示了一类新型的易于保存的试剂——糖基硒磺酸盐的设计，它独特地将自由基反应性与亲电性质相结合，从而在温和的反应条件下便于直接引入糖基硒部分。光照后，炔烃与糖基硒磺酸盐的自由基加成反应速率极快，不到1分钟即可完成。同样，含半胱氨酸分子的功能化在相当短的时间内即可实现，大多数情况下通常在1分钟内完成。涉及各种氨基酸的添加剂实验证实了这些转化的稳健性，表明在不同的反应环境中始终具有高效率且干扰可忽略不计。重要的是，在水性条件下成功进行肽和蛋白质标记突出了该方法在生物正交应用方面的潜力。这些发现共同强调了糖基硒磺酸盐在开发用于生物和化学研究的快速高效标记技术方面的广泛适用性和操作简便性。这项工作不仅推动了糖基硒支架的合成方法，还为复杂生物系统的功能研究开辟了新途径。
