ArticleNature chemistry2019
A synthetic genetic polymer with an uncharged backbone chemistry based on alkyl phosphonate nucleic acids.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Single-residue engineering of Klenow fragment enables broad acceptance of chemically modified nucleotides.Nucleic acids research · 2026Article
- Macrophages Intracellularly Gelated With Bioactive Hydrogels for Synergistic Neutralization, Eradication, and Osteopromotion in Periodontitis Treatment.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Are we there yet with XNA aptamers?RSC advances · 2026Review
- Enzymatic Synthesis of Mixed XNA Polymers Containing 2'Fluoro and 2'Azide Modifications.ACS omega · 2025Article
- Engineering a Thermostable Reverse Transcriptase for RT-PCR Through Rational Design ofBiomolecules · 2025Article
- Physicochemical Properties of PhosphoramideACS omega · 2025Article
- Astrobiological implications of the stability and reactivity of peptide nucleic acid (PNA) in concentrated sulfuric acid.Science advances · 2025Article
- A system for in vitro selection of fully 2'-modified RNA aptamers.Organic & biomolecular chemistry · 2025Article
- Aptamer and DNAzyme Based Colorimetric Biosensors for Pathogen Detection.Angewandte Chemie (International ed. in English) · 2025Review
- Recent advances in aptamer discovery, modification and improving performance.Biochemistry and biophysics reports · 2024Review
- Review
- Synthesis and Properties of α-Phosphate-Modified Nucleoside Triphosphates.Molecules (Basel, Switzerland) · 2024Review
- A Visual Compendium of Principal Modifications within the Nucleic Acid Sugar Phosphate Backbone.Molecules (Basel, Switzerland) · 2024Review
- Controlled enzymatic synthesis of oligonucleotides.Communications chemistry · 2024Review
- Direct Enzyme Engineering of B Family DNA Polymerases for Biotechnological Approaches.Bioengineering (Basel, Switzerland) · 2023Review
- Characterization of an HNA aptamer suggests a non-canonical G-quadruplex motif.Nucleic acids research · 2023Article
- The Expanded Central Dogma: Genome Resynthesis, Orthogonal Biosystems, Synthetic Genetics.Annual review of biophysics · 2023Review
- Accessible light-controlled knockdown of cell-free protein synthesis using phosphorothioate-caged antisense oligonucleotides.Communications chemistry · 2023Article
- Nucleic acid nanostructures forApplied physics reviews · 2023Review
- Chemically modified aptamers for improving binding affinity to the target proteinsFrontiers in cell and developmental biology · 2023Review
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Abstract
The physicochemical properties of nucleic acids are dominated by their highly charged phosphodiester backbone chemistry. This 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 (phNAs) in which the canonical, negatively charged phosphodiester is replaced by an uncharged P-alkyl phosphonodiester 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 an 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.
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