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

机译:Copper-Catalyzed Huisgen 1,3 -偶极环加成反应针对Phosphorothioate寡核苷酸

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Karolinska Institutet, Department of Biosciences and Nutrition, Huddinge, Sweden Corresponding authors: malgorzata.honcharenko@ki.se; roger.stromberg@ki.seAn 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 x Me_2S) 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 x Me_2S.
机译:卡罗林斯卡医学院,生物科学和营养,Huddinge、瑞典对应作者:malgorzata.honcharenko@ki.se;roger.stromberg@ki.seAn有效方法附件的各种记者团体寡核苷酸(ONs)是铜(I)(铜(I))催化Huisgen azide-alkyne1,3 -偶极环加成反应(“点击反应”)。然而,在与phosphorothioate ONs的情况修改为internucleosidic联系(PS-ONs),这种结合方法调整是兼容的含硫组。这是用于PS-ONs,利用solid-supported ONs,实现了铜(I)溴二甲基硫醚复杂(CuBr x Me_2S)点击反应作为调停者。solid-supported ONs很容易改变到“点击ONs”在线添加一个随后alkyne-containing链接器,可以与一个反应azido-containing一半(比如,一个肽)CuBr x Me_2S的存在。

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