Kitoun Camélia, Fonvielle Matthieu, Sakkas Nicolas, Lefresne Manon, Djago Fabiola, Blancart Remaury Quentin, Poinot Pauline, Arthur Michel, Etheve-Quelquejeu Mélanie, Iannazzo Laura
UMR CNRS 8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université de Paris, F-75006 Paris, France.
INSERM, Sorbonne Université, Université de Paris, Centre de Recherche des Cordeliers (CRC), F-75006, Paris, France.
Org Lett. 2020 Oct 16;22(20):8034-8038. doi: 10.1021/acs.orglett.0c02982. Epub 2020 Sep 30.
Staudinger ligation is an attractive bio-orthogonal reaction that has been widely used to tag proteins, carbohydrates, and nucleic acids. Here, we explore the traceless variant of the Staudinger ligation for 3'-end modification of oligoribonucleotides. An azido-containing dinucleotide was used to study the ligation. Nine phosphines containing reactive groups, affinity purification tags, or photoswitch probes have been successfully obtained. The corresponding modified dinucleotides were synthesized and characterized by LC/MS. Mechanistic interpretations of the reaction are proposed, in particular, the unprecedented formation of an oxazaphospholane nucleotide derivative, which was favored by the vicinal position of 2'-N and 3'-OH functional groups on the terminal ribose has been observed. The post-functionalization of a 24-nt RNA with a photoactivable tag is also reported.
施陶丁格连接反应是一种颇具吸引力的生物正交反应，已被广泛用于标记蛋白质、碳水化合物和核酸。在此，我们探索施陶丁格连接反应的无痕变体用于寡核糖核苷酸的3'端修饰。使用一种含叠氮基的二核苷酸来研究连接反应。已成功获得九种含有反应性基团、亲和纯化标签或光开关探针的膦。合成了相应的修饰二核苷酸，并通过液相色谱/质谱进行了表征。提出了该反应的机理解释，特别是观察到了恶唑磷杂环戊烷核苷酸衍生物的前所未有的形成，末端核糖上2'-N和3'-OH官能团的邻位有利于这种形成。还报道了用可光激活标签对24个核苷酸的RNA进行后功能化修饰。
