专为硫代寡核苷酸设计的铜催化Huisgen 1,3-偶极环加成

Q4 Chemistry

Current Protocols in Nucleic Acid Chemistry Pub Date : 2019-12-29 DOI:10.1002/cpnc.102

Malgorzata Honcharenko, Dmytro Honcharenko, Roger Stromberg

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引用次数: 1

摘要

铜(I) [Cu(I)]催化的Huisgen叠氮- 1,3-炔偶极环加成反应(“click反应”)是一种将多种报告基团连接到寡核苷酸(ONs)上的有效方法。然而，对于具有硫代修饰的核苷间键(PS-ONs)的离子，必须调整这种缀合方法以与含硫基团相容。本文描述的方法适用于PS-ONs，利用固体负载的ONs，并实现了Cu(I)溴化二甲基硫化配合物(CuBr × Me2S)作为点击反应的介质。通过在线添加含炔的连接剂，固体支撑的离子可以很容易地转化为“可点击的离子”，该连接剂随后可以在CuBr × Me2S存在下与含叠氮基团的部分(例如肽)反应。©2019 by John Wiley &基本方案1:固体支架上的偶联;支持方案:从氨基连接物上去除4,4 ' -二甲氧基三硝基;基本方案2:从固体支架上去除保护基团和裂解;基本方案3:高效液相色谱纯化

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Copper-Catalyzed Huisgen 1,3-Dipolar Cycloaddition Tailored for Phosphorothioate Oligonucleotides

An efficient method for attachment of a variety of reporter groups to oligonucleotides (ONs) is copper (I) [Cu(I)]-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (“click reaction”). However, in the case of ONs with phosphorothioate modifications as internucleosidic linkages (PS-ONs), this conjugation method has to be adjusted to be compatible with the sulfur-containing groups. The method described here is adapted for PS-ONs, utilizes solid-supported ONs, and implements the Cu(I) bromide dimethyl sulfide complex (CuBr × Me₂S) as a mediator for the click reaction. The solid-supported ONs can be readily transformed into “clickable ONs” by on-line addition of an alkyne-containing linker that subsequently can react with an azido-containing moiety (e.g., a peptide) in the presence of CuBr × Me₂S. © 2019 by John Wiley & Sons, Inc.

Basic Protocol 1: Conjugation on solid support

Support Protocol: Removal of 4,4′-dimethoxytrityl group from amino linker

Basic Protocol 2: Removal of protecting groups and cleavage from solid support

Basic Protocol 3: HPLC purification

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来源期刊

Current Protocols in Nucleic Acid Chemistry Chemistry-Organic Chemistry

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期刊介绍： Published in association with International Society for Nucleosides, Nucleotides & Nucleic Acids (IS3NA) , Current Protocols in Nucleic Acid Chemistry is equally valuable for biotech, pharmaceutical, and academic labs. It is the resource for designing and running successful research projects in the rapidly growing and changing field of nucleic acid, nucleotide, and nucleoside research.