A High-Fidelity Codon Set for the T4 DNA Ligase-Catalyzed Polymerization of Modified Oligonucleotides
A High-Fidelity Codon Set for the T4 DNA Ligase-Catalyzed Polymerization of Modified Oligonucleotides
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DOI：
10.1021/acscombsci.5b00119
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发表时间：
2015-12-01
影响因子：
--
通讯作者：
Hili, Ryan
中科院分区：
文献类型：
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作者：
Lei, Yi;Kong, Dehui;Hili, Ryan
核酸聚合物的体外选择可以容易地递送用于各种应用的高度特异性受体和催化剂;然而，怀疑核酸的官能团缺陷限制了它们在蛋白质聚合物方面的潜力。这刺激了对扩大其化学多样性的研究，以弥合核酸和蛋白质之间的功能差距，从而开发出上级生物聚合物。在这项研究中，我们调查的影响密码子库的大小和组成的T4 DNA连接酶的序列特异性的DNA模板聚合的未修饰和修饰的寡核苷酸。使用双链体对的高通量DNA测序，我们已经发现了一个256元密码子组，该密码子组以高产率和高保真度产生序列定义的修饰的ssDNA聚合物。
In vitro selection of nucleic acid polymers can readily deliver highly specific receptors and catalysts for a variety of applications; however, it is suspected that the functional group deficit of nucleic acids has limited their potential with respect to proteinogenic polymers. This has stimulated research toward expanding their chemical diversity to bridge the functional gap between nucleic acids and proteins to develop a superior biopolymer. In this study, we investigate the effect of codon library size and composition on the sequence specificity of T4 DNA ligase in the DNA-templated polymerization of both unmodified and modified oligonucleotides. Using high-throughput DNA sequencing of duplex pairs, we have uncovered a 256-membered codon set that yields sequence-defined modified ssDNA polymers in high yield and with high fidelity.