Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 42, Pages 13164-13168Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201607538
Keywords
ligase; modified DNA; molecular evolution; nucleic acids; sequencing
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Funding
- National Institutes of Health [R21CA207711]
- Office for the Vice President of Research, University of Georgia
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The development and in-depth analysis of T4 DNA ligase-catalyzed DNA templated oligonucleotide polymerization toward the generation of diversely functionalized nucleic acid polymers is described. The NNNNT codon set enables low codon bias, high fidelity, and high efficiency for the polymerization of ANNNN libraries comprising various functional groups. The robustness of the method was highlighted in the copolymerization of a 256-membered ANNNN library comprising 16 sub-libraries modified with different functional groups. This enabled the generation of diversely functionalized synthetic nucleic acid polymer libraries with 93.8% fidelity. This process should find ready application in DNA nano-technology, DNA computing, and in vitro evolution of functional nucleic acid polymers.
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