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2019-04-22

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/132998

A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids

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http://dx.doi.org/10.1038/s41557-019-0255-4

Resum

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.

Matèries

Polímers, Àcids nucleics

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Polymers, Nucleic acids

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Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

ARANGUNDY-FRANKLIN, Sebastian, TAYLOR, Alexander i., POREBSKI, Benjamin t., GENNA, Vito, PEAK-CHEW, Sew, VAISMAN, Alexandra, WOODGATE, Roger, OROZCO LÓPEZ, Modesto, HOLLIGER, Philipp. A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids. _Nature Chemistry_. 2019. Vol. 11, núm. 533–542. [consulta: 20 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/132998]

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