Aptamers, which are polymers composed of single-stranded nucleic acids, are capable of binding target molecules with both high affinity and specificity. However, compared with the twenty natural occurring amino acids present in proteins, only four canonical bases are available for DNA aptamers. The T4 DNA ligase-catalyzed DNA-templated polymerization of 5’-phosphrylated oligonucleotides has expanded this limitation. The incorporation of various functionalities is achieved by the sequence-defined polymerization of modified oligonucleotides along a DNA template. Thus, the diversity of functionalities depends on the codon length instead of the number of single bases. Here described is the in-depth analysis of T4 DNA ligase-catalyzed polymerization of various codon length, library codon size, and codon sequences. The NNNNT codon set was found to enable low codon bias, high fidelity, and high efficiency, all the while tolerating a broad scope of chemical functionality. Its application to the <i>in vitro</i> evolution of modified aptamers towards glycan molecule recognition is also described.

T4 DNA ligase-catalyzed polymerization of modified oligonucleotides: Discovery and application of a high-fidelity codon set to the evolution of modified aptamers

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.