Lei Yi, Kong Dehui, Hili Ryan
Department of Chemistry, University of Georgia , 140 Cedar Street, Athens, Georgia 30602, United States.
ACS Comb Sci. 2015 Dec 14;17(12):716-21. doi: 10.1021/acscombsci.5b00119. Epub 2015 Nov 12.
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.
核酸聚合物的体外筛选能够轻松为各种应用提供高度特异性的受体和催化剂；然而，有人怀疑核酸的官能团缺陷限制了它们相对于蛋白质聚合物的潜力。这激发了相关研究，旨在扩大其化学多样性，以弥合核酸与蛋白质之间的功能差距，从而开发出一种更优质的生物聚合物。在本研究中，我们研究了密码子文库大小和组成对T4 DNA连接酶在未修饰和修饰寡核苷酸的DNA模板聚合反应中序列特异性的影响。通过对双链体对进行高通量DNA测序，我们发现了一个由256个成员组成的密码子集，该密码子集能够以高产率和高保真度产生序列定义的修饰单链DNA聚合物。
