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Title: | A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids |
Author: | Arangundy-Franklin, Sebastian Taylor, Alexander I. Porebski, Benjamin T. Genna, Vito Peak-Chew, Sew Vaisman, Alexandra Woodgate, Roger Orozco López, Modesto Holliger, Philipp |
Keywords: | Polímers Àcids nucleics Polymers Nucleic acids |
Issue Date: | 22-Apr-2019 |
Publisher: | Nature Publishing Group |
Abstract: | The physicochemical properties of nucleic acids are dominated by their highly charged phosphodiester backbone chemistry. The polyelectrolyte structure decouples information content (base sequence) from bulk properties such as solubility and has been proposed as a defining trait of all informational polymers. However, this conjecture has not been tested experimentally. Here, we describe the encoded synthesis of a genetic polymer with an uncharged backbone chemistry: alkyl-phosphonate nucleic acids (phNA), in which the canonical, negatively charged phosphodiester is replaced by an uncharged P-alkylphosphonodiester backbone. Using synthetic chemistry and polymerase engineering, we describe the enzymatic, DNA-templated synthesis of P-methyl- and P-ethyl-phNAs, and the directed evolution of specific streptavidin-binding phNA aptamer ligands directly from random-sequence, mixed P-methyl- / P-ethyl-phNA repertoires. Our results establish a first example of the DNA-templated enzymatic synthesis and evolution of an uncharged genetic polymer and provide a foundational methodology for their exploration as a source of novel, functional molecules. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1038/s41557-019-0255-4 |
It is part of: | Nature Chemistry, 2019, vol. 11, p. 533–542 |
URI: | http://hdl.handle.net/2445/132998 |
Related resource: | http://dx.doi.org/10.1038/s41557-019-0255-4 |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
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696262.pdf | 71.35 MB | Adobe PDF | View/Open |
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