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Oligonucleotide tagging for copper-free click conjugation.

ABSTRACT: Copper-free click chemistry between cyclooctynes and azide is a mild, fast and selective technology for conjugation of oligonucleotides. However, technology for site-specific introduction of the requisite probes by automated protocols is scarce, while the reported cyclooctynes are large and hydrophobic. In this work, it is demonstrated that the introduction of bicyclo[6.1.0]nonyne (BCN) into synthetic oligonucleotides is feasible by standard solid-phase phosphoramidite chemistry. A range of phosphoramidite building blocks is presented for incoporation of BCN or azide, either on-support or in solution. The usefulness of the approach is demonstrated by the straightforward and high-yielding conjugation of the resulting oligonucleotides, including biotinylation, fluorescent labeling, dimerization and attachment to polymer.

SUBMITTER: Jawalekar AM

PROVIDER: S-EPMC6270431 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Oligonucleotide tagging for copper-free click conjugation.

Jawalekar Anup M AM Malik Sudip S Verkade Jorge M M JM Gibson Brian B Barta Nancy S NS Hodges John C JC Rowan Alan A van Delft Floris L FL

Molecules (Basel, Switzerland) 20130624 7

Copper-free click chemistry between cyclooctynes and azide is a mild, fast and selective technology for conjugation of oligonucleotides. However, technology for site-specific introduction of the requisite probes by automated protocols is scarce, while the reported cyclooctynes are large and hydrophobic. In this work, it is demonstrated that the introduction of bicyclo[6.1.0]nonyne (BCN) into synthetic oligonucleotides is feasible by standard solid-phase phosphoramidite chemistry. A range of phos ...[more]

PMID: 23884112

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