DNA Ligase-Mediated Translation of DNA Into Densely Functionalized Nucleic Acid Polymers
Open Access
- 26 December 2012
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 135 (1), 98-101
- https://doi.org/10.1021/ja311331m
Abstract
We developed a method to translate DNA sequences into densely functionalized nucleic acids by using T4 DNA ligase to mediate the DNA-templated polymerization of 5′-phosphorylated trinucleotides containing a wide variety of appended functional groups. This polymerization proceeds sequence specifically along a DNA template and can generate polymers of at least 50 building blocks (150 nucleotides) in length with remarkable efficiency. The resulting single-stranded highly modified nucleic acid is a suitable template for primer extension using deep vent (exo-) DNA polymerase, thereby enabling the regeneration of template DNA. We integrated these capabilities to perform iterated cycles of in vitro translation, selection, and template regeneration on libraries of modified nucleic acid polymers.Keywords
Funding Information
- Natural Sciences and Engineering Research Council of Canada
- National Institute of General Medical Sciences
- Howard Hughes Medical Institute
- Eli Lilly and Company
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