Department of Process Chemistry , Merck & Co. Inc. , Rahway , New Jersey 07065 , United States.
Bioconjug Chem. 2018 Jun 20;29(6):1859-1865. doi: 10.1021/acs.bioconjchem.8b00298. Epub 2018 Jun 12.
An efficient multicomponent orthogonal protocol was developed for post-synthetic oligonucleotide modification using commercially available 2'- O-methyl ester and 2'- O-propargyl nucleoside scaffolds. Amidation of methyl esters with primary amines was achieved in the presence of 2'-propargyl groups which were utilized for subsequent copper catalyzed cycloaddition with GalNAc-azide. The methodology was applied to generate siRNA composed of multiple amide and triazole conjugates. Computational methods were used to illustrate the impact of substitution at the 2'-position. This a powerful post-oligomerization technique for rapidly introducing diversity to oligonucleotide design.
开发了一种高效的多组分正交方案，用于使用市售的 2'-O-甲酯和 2'-O-炔丙基核苷支架进行合成后寡核苷酸修饰。在存在 2'-炔丙基基团的情况下，甲酯与伯胺发生酰胺化反应，随后用于与 GalNAc-叠氮化物进行后续的铜催化环加成反应。该方法用于生成由多个酰胺和三唑缀合物组成的 siRNA。计算方法用于说明 2'-位取代的影响。这是一种强大的聚合后技术，可快速将多样性引入寡核苷酸设计中。
