A New Architecture for DNA-Templated Synthesis in Which Abasic Sites Protect Reactants from Degradation.

A New Architecture for DNA-Templated Synthesis in Which Abasic Sites Protect Reactants from Degradation.
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DNA 模板合成的新架构,其中无碱基位点可保护反应物免遭降解。

DOI:
10.1002/anie.202317482
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发表时间:
2024
期刊:
Angewandte Chemie (International ed. in English)
影响因子:
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通讯作者:
Frommer J
Frommer J
中科院分区:
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文献类型:
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作者:
Frommer J

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人工序列定义的聚合物的合成,匹配和扩展蛋白质的功能是材料科学的一个重要目标。实现这一点的一种方式是通过连接的寡核苷酸衔接子来编程前体构件之间的化学反应序列。然而,到目前为止,反应性结构单元的水解限制了可以使用DNA模板化反应获得的产物的长度和产率。在这里,我们报告了一种DNA模板合成的体系结构,其中反应物被拴在DNA双链体相对链上的内部脱碱基位点。我们发现,DNA双链体中的脱碱基位点可以保护附近的硫酯免受降解,从而显着提高DNA模板反应的产率。这种保护作用有可能通过延长反应性结构单元的寿命来克服与长非天然聚合物的可编程、序列控制合成相关的挑战。
The synthesis of artificial sequence‐defined polymers that match and extend the functionality of proteins is an important goal in materials science. One way of achieving this is to program a sequence of chemical reactions between precursor building blocks by means of attached oligonucleotide adapters. However, hydrolysis of the reactive building blocks has so far limited the length and yield of product that can be obtained using DNA‐templated reactions. Here, we report an architecture for DNA‐templated synthesis in which reactants are tethered at internal abasic sites on opposite strands of a DNA duplex. We show that an abasic site within a DNA duplex can protect a nearby thioester from degradation, significantly increasing the yield of a DNA‐templated reaction. This protective effect has the potential to overcome the challenges associated with programmable, sequence‐controlled synthesis of long non‐natural polymers by extending the lifetime of the reactive building blocks.