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Molecules 2013, 18(7), 7346-7363; doi:10.3390/molecules18077346

Oligonucleotide Tagging for Copper-Free Click Conjugation

Received: 19 April 2013 / Revised: 24 May 2013 / Accepted: 5 June 2013 / Published: 24 June 2013
(This article belongs to the Section Organic Synthesis)
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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.
Keywords: copper-free click; oligonucleotide conjugation; bicyclononyne; azide; strain-promoted cycloaddition copper-free click; oligonucleotide conjugation; bicyclononyne; azide; strain-promoted cycloaddition
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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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.

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