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Enzymatic Synthesis of Sequence‐Defined Synthetic Nucleic Acid Polymers with Diverse Functional Groups
Author(s) -
Kong Dehui,
Lei Yi,
Yeung Wayland,
Hili Ryan
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201607538
Subject(s) - nucleic acid , oligonucleotide , dna , functional polymers , polymer , polymerization , combinatorial chemistry , dna ligase , deoxyribozyme , nucleic acid analogue , chemistry , biochemistry , nucleic acid thermodynamics , organic chemistry , base sequence
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 nanotechnology, DNA computing, and in vitro evolution of functional nucleic acid polymers.