Biocompatible SuFEx Click Chemistry: Thionyl Tetrafluoride (SOF4)-Derived Connective Hubs for Bioconjugation to DNA and Proteins
Biocompatible SuFEx Click Chemistry: Thionyl Tetrafluoride (SOF4)-Derived Connective Hubs for Bioconjugation to DNA and Proteins
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DOI：
10.1002/anie.201902489
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发表时间：
2019-06-11
影响因子：
16.6
通讯作者：
Sharpless, K. Barry
中科院分区：
文献类型：
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作者：
Liu, Feng;Wang, Hua;Sharpless, K. Barry
我们在此报告了在水性缓冲液条件下从 SOF4 衍生的亚氨基硫二氟化物中心开发出一套生物相容性 SuFEx 转化。亚氨基二氟化硫 (R-N=SOF2) 与伯胺的这些生物相容性 SuFEx 反应生成磺酰胺（8 个示例，高达 98%），而与仲胺的反应则提供磺酰亚胺酰氟产品（8 个示例，高达 97%）。同样，在温和的缓冲条件下，苯酚与亚氨基硫二氟化物 (Ar-N=SOF2) 反应生成硫代氟亚氨酸酯（13 个例子，高达 99%），其本身可以被亲核试剂进一步修饰。这些转变开启了从硫 (VI) 中心突出的不对称和三取代连接的潜力，包括多功能的 S-N 和 S-O 连接（9 个例子，高达 94%）。最后，亚氨基二氟化硫与胺标记的单链 DNA 和 BSA 蛋白的 SuFEx 生物共轭证明了 SOF4 衍生的 SuFEx 点击化学在生物应用中的潜力。
We report here the development of a suite of biocompatible SuFEx transformations from the SOF4-derived iminosulfur oxydifluoride hub in aqueous buffer conditions. These biocompatible SuFEx reactions of iminosulfur oxydifluorides (R-N=SOF2) with primary amines give sulfamides (8 examples, up to 98 %), while the reaction with secondary amines furnish sulfuramidimidoyl fluoride products (8 examples, up to 97 %). Likewise, under mild buffered conditions, phenols react with the iminosulfur oxydifluorides (Ar-N=SOF2) to produce sulfurofluoridoimidates (13 examples, up to 99 %), which can themselves be further modified by nucleophiles. These transformations open the potential for asymmetric and trisubstituted linkages projecting from the sulfur(VI) center, including versatile S-N and S-O connectivity (9 examples, up to 94 %). Finally, the SuFEx bioconjugation of iminosulfur oxydifluorides to amine-tagged single-stranded DNA and to BSA protein demonstrate the potential of SOF4-derived SuFEx click chemistry in biological applications.