Novel amino linkers enabling efficient labeling and convenient purification of amino-modified oligonucleotides
Novel amino linkers enabling efficient labeling and convenient purification of amino-modified oligonucleotides
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DOI：
10.1016/j.bmc.2007.10.011
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发表时间：
2008-01-15
影响因子：
3.5
通讯作者：
Ohtsuka, Eiko
中科院分区：
文献类型：
--
作者：
Komatsu, Yasuo;Kojima, Naoshi;Ohtsuka, Eiko
我们为寡核苷酸 (ONT) 末端开发了新的氨基连接试剂。这些试剂由氨基乙基氨基甲酸酯主键和侧链残基组成，侧链残基为萘基甲氧基甲基、甲氧基甲基或甲基或氢原子。伯胺用单甲氧基三苯甲基（MMT）基团保护。研究了含有这些氨基修饰的 ONT 的化学性质。这些氨基修饰的 MMT 基团可以在非常温和的酸性条件下从胺中快速去除，而酸性条件对于常规脂肪胺的脱保护来说不够强。这一显着特征使得氨基修饰的 ONT 可以方便地用反相柱纯化。此外，与其他氨基修饰相比，氨基修饰可以有效地与活性酯反应。我们还发现氨基修饰的 pK(a) 值低于脂肪胺的 pK(a) 值。所有的实验结果表明这些化学性质与其结构密切相关。我们在这里报告了新型氨基连接试剂的化学性质和可用性。 (C) 2007 Elsevier Ltd. 保留所有权利。
We developed new amino linker reagents for an oligonucleotide (ONT) terminus. These reagents consist of an aminoethyl carbamate main linkage and a side-chain residue, which was a naphthylmethoxymethyl, methoxymethyl, or methyl group or a hydrogen atom. The primary amine was protected with a monomethoxytrityl (MMT) group. The chemical properties of ONTs containing these amino-modifications were investigated. The MMT group of these amino-modifications could be quite rapidly removed from the amine under very mild acidic conditions, which are not strong enough for the deprotection of a conventional aliphatic amine. This significant feature enabled the amino-modified ONTs to be conveniently purified with a reverse phase column. Furthermore, the amino-modifications efficiently reacted to active esters, as compared with other amino-modifications. We also found that the pK(a), values of the amino-modifications were lower than that of the aliphatic amine. All of the experimental results showed that these chemical properties are closely related to their structures. We report here the chemical properties and the availability of the new amino linker reagents. (C) 2007 Elsevier Ltd. All rights reserved.