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.
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Jawalekar, A.M.; Malik, S.; Verkade, J.M.M.; Gibson, B.; Barta, N.S.; Hodges, J.C.; Rowan, A.; van Delft, F.L. Oligonucleotide Tagging for Copper-Free Click Conjugation. Molecules 2013, 18, 7346-7363.
Jawalekar AM, Malik S, Verkade JMM, Gibson B, Barta NS, Hodges JC, Rowan A, van Delft FL. Oligonucleotide Tagging for Copper-Free Click Conjugation. Molecules. 2013; 18(7):7346-7363.
Jawalekar, Anup M.; Malik, Sudip; Verkade, Jorge M.M.; Gibson, Brian; Barta, Nancy S.; Hodges, John C.; Rowan, Alan; van Delft, Floris L. 2013. "Oligonucleotide Tagging for Copper-Free Click Conjugation." Molecules 18, no. 7: 7346-7363.