Facilitated Synthetic Access to Boronic Acid-Modified Nucleoside Triphosphates and Compatibility with Enzymatic DNA Synthesis

Germain Niogret; Pascal Röthlisberger; Fabienne Levi-Acobas; Frédéric Bonhomme; Gilles Gasser; Marcel Hollenstein

doi:10.1055/a-2212-7704

Synlett, Table of Contents

Synlett 2024; 35(06): 677-683
DOI: 10.1055/a-2212-7704

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Special Issue to Celebrate the Centenary Year of Prof. Har Gobind Khorana

Facilitated Synthetic Access to Boronic Acid-Modified Nucleoside Triphosphates and Compatibility with Enzymatic DNA Synthesis

Germain Niogret‡

^aInstitut Pasteur, Université Paris Cité, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France

^cChimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005 Paris, France

,

Pascal Röthlisberger ‡

^aInstitut Pasteur, Université Paris Cité, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France

,

Fabienne Levi-Acobas

^aInstitut Pasteur, Université Paris Cité, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France

,

Frédéric Bonhomme

^bInstitut Pasteur, Université Paris Cité, Department of Structural Biology and Chemistry, Unité de Chimie Biologique Epigénétique, UMR CNRS 3523, 28 rue du Docteur Roux, CEDEX 15, 75724 Paris, France

,

Gilles Gasser

^cChimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005 Paris, France

,

Marcel Hollenstein ∗

^aInstitut Pasteur, Université Paris Cité, Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France

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Abstract

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Abstract

Decorating nucleic acids with boronic acids can extend the usefulness of oligonucleotide-based tools to the development of medical imaging agents, the promotion of binding of aptamers to markedly more challenging targets, or the detection of (poly)saccharides. However, due to the hygroscopic nature and high intrinsic reactivity of boronic acids, protocols for their introduction into nucleic acids are scarce. Here, we have explored various synthetic routes for the crafting of nucleoside triphosphates equipped with phenylboronic acids. Strain-promoted azide–alkyne cycloaddition appears to be the method of choice for this purpose and it enabled us to prepare a modified nucleotide. Enzymatic DNA synthesis permitted the introduction of up to thirteen boronic acid residues in oligonucleotides, which bodes well for its extension to SELEX and related methods of in vitro selection of functional nucleic acids.

Key words

nucleoside triphosphates - click chemistry - DNA - boron chemistry - SELEX

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References

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