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

Decorating nucleic acids with boronic acids can extend theusefulness of oligonucleotide-based tools to the development of medi-cal imaging agents, the promotion of binding of aptamers to markedlymore challenging targets, or the detection of (poly)saccharides. How-ever, due to the hygroscopic nature and high intrinsic reactivity of bo-ronic acids, protocols for their introduction into nucleic acids are scarce.Here, we have explored various synthetic routes for the crafting of nu-cleoside triphosphates equipped with phenylboronic acids. Strain-pro-moted azide-alkyne cycloaddition appears to be the method of choicefor this purpose and it enabled us to prepare a modified nucleotide. En-zymatic DNA synthesis permitted the introduction of up to thirteen bo-ronic acid residues in oligonucleotides, which bodes well for its exten-sion to SELEX and related methods of in vitro selection of functionalnucleic acids.