Direct, solid phase assembly of dihydropyrroloindole peptides with conjugated oligonucleotides.
Direct, solid phase assembly of dihydropyrroloindole peptides with conjugated oligonucleotides.
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二氢吡咯并吲哚肽与缀合寡核苷酸的直接固相组装。
DOI：
10.1021/bc960041d
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Meyer,RB
中科院分区：
文献类型：
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作者：
Lukhtanov,EA;Kutyavin,IV;Meyer,RB
描述了一种新的可控孔玻璃（CPG）载体，其允许直接合成在3 '-末端携带小沟结合（MGB）剂的寡核苷酸衍生物。MGB由三个重复的1，2-二氢-3H-吡咯并[2，3-e]吲哚-7-羧酸（DPI）亚基组成。使用重复添加DPI亚基直接在CPG载体上制备DPI三聚体（DPI 3）。亚基的N −3位被叔丁氧羰基保护，7位羧基被2，3，5，6-四氟苯基酯化而活化。通过末端N −3与4-[bis（4-methoxyphenyl）phenylmethoxy]butyrate对硝基苯基酯反应，引入了为寡核苷酸合成提供起始点的接头。当用作寡核苷酸合成的载体时，这种修饰的CPG以良好的产率得到所需的3 '-DPI 3 −八胸苷酸[（dTp）8-DPI 3]缀合物。该缀合物与互补的多核糖-（Tmax= 35 °C）和多脱氧核糖腺苷酸（Tmax= 69 °C）形成超稳定复合物。与我们以前报道的N-氨基甲酰基衍生物相比，它表现出更高的熔融转变协同性。
A new controlled pore glass (CPG) support is described that allows for the direct synthesis of oligonucleotide derivatives carrying a minor groove binding (MGB) agent at the 3‘-terminus. The MGB consisted of three repeating 1,2-dihydro-3H-pyrrolo[2,3-e]indole-7-carboxylate (DPI) subunits. The DPI trimer (DPI3) was prepared directly on the CPG support using repeated addition of the DPI subunit. The subunit was protected at theN−3-position withtert-butyloxycarbonyl residue and activated at the 7-carboxy residue by esterification with the 2,3,5,6-tetrafluorophenyl group. A linker, which provided the starting point for oligonucleotide synthesis, was introduced by reaction of the terminalN−3 withp-nitrophenyl 4-[bis(4-methoxyphenyl)phenylmethoxy]butyrate. When used as a support for oligonucleotide synthesis, this modified CPG gave the desired 3‘-DPI3−octathymidylate [(dTp)8-DPI3] conjugate in good yield. This conjugate formed hyperstabilized complexes with complementary polyribo- (Tmax= 35 °C) and polydeoxyriboadenylic (Tmax= 69 °C) acids. In contrast to theN-carbamoyl derivative reported earlier by us, it demonstrated higher cooperativity of melting transitions.