Keil Joseph M, Chan Ka Keung, Sun Xue-Long
Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115, United States.
Polym Chem. 2024 May 14;15(18):1884-1896. doi: 10.1039/d4py00191e. Epub 2024 Apr 11.
Glycopolymers have been employed as biomimetic glycoconjugates in both biological and biomedical research and applications. Among them, chain-end functionalized glycopolymers are very often explored for protein modification, microarray, biosensor, bioprobe and other applications. Herein, we report a straightforward synthesis of α,ω-end orthogonally functionalizable glycopolymers. Specifically, glycopolymers with an alkyne or azide group at one end and an -cyanate on the other end were synthesized cyanoxyl-mediated free-radical polymerization from native glycans without protection and deprotection. The alkyne chain-end can react with azide-containing molecules click chemistry. The azide chain-end can react with alkyne-containing molecules click chemistry or copper free click chemistry. On the other hand, -cyanate can react with an amine group isourea bond, affording a site-specific bioconjugation as well. Furthermore, chain-end heterofunctionalizations of the glycopolymers were demonstrated sequential or one-pot click chemistry and isourea bond formation, respectively. Finally, end-to-end dimerization of the glycopolymers was demonstrated chain-end click chemistry. These α,ω-end orthogonally functionalizable glycopolymers will be useful in many biological and biomedical research applications.
糖聚合物已被用作生物和生物医学研究及应用中的仿生糖缀合物。其中，链端功能化糖聚合物经常被用于蛋白质修饰、微阵列、生物传感器、生物探针及其他应用的研究。在此，我们报道了一种直接合成α,ω-端可正交功能化糖聚合物的方法。具体而言，通过氰氧基介导的自由基聚合反应，从天然聚糖出发，无需保护和脱保护步骤，合成了一端带有炔基或叠氮基、另一端带有异氰酸酯基的糖聚合物。炔基链端可通过点击化学与含叠氮基的分子发生反应。叠氮基链端可通过点击化学或无铜点击化学与含炔基的分子发生反应。另一方面，异氰酸酯基可与胺基反应形成异脲键，也能实现位点特异性生物共轭。此外，分别通过顺序点击化学或一锅法点击化学以及异脲键形成反应，证明了糖聚合物的链端异官能化。最后，通过链端点击化学证明了糖聚合物的端到端二聚化。这些α,ω-端可正交功能化糖聚合物将在许多生物和生物医学研究应用中发挥作用。
