Drug Discovery, Alnylam Pharmaceuticals, Cambridge, Massachusetts 02142, USA.
Org Lett. 2010 Dec 3;12(23):5410-3. doi: 10.1021/ol102205j. Epub 2010 Nov 4.
Novel non-nucleoside alkyne monomers compatible with oligonucleotide synthesis were designed, synthesized, and efficiently incorporated into RNA and RNA analogues during solid-phase synthesis. These modifications allowed site-specific conjugation of ligands to the RNA oligonucleotides through copper-assisted (CuAAC) and copper-free strain-promoted azide-alkyne cycloaddition (SPAAC) reactions. The SPAAC click reactions of cyclooctyne-oligonucleotides with various classes of azido-functionalized ligands in solution phase and on solid phase were efficient and quantitative and occurred under mild reaction conditions. The SPAAC reaction provides a method for the synthesis of oligonucleotide-ligand conjugates uncontaminated with copper ions.
设计、合成了与寡核苷酸合成兼容的新型非核苷炔烃单体，并在固相合成中有效地将其掺入 RNA 和 RNA 类似物中。这些修饰允许通过铜辅助（CuAAC）和无铜应变促进的叠氮化物-炔烃环加成（SPAAC）反应将配体特异性地连接到 RNA 寡核苷酸上。在溶液相和固相中环辛炔寡核苷酸与各种类别的叠氮功能化配体的 SPAAC 点击反应是高效和定量的，并且在温和的反应条件下发生。SPAAC 反应为合成无铜离子污染的寡核苷酸-配体缀合物提供了一种方法。
