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Oligonucleotide Tagging for Copper-Free Click Conjugation
Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands
SynAffix BV, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands
Berry and Associates, Inc., 2434 Bishop Circle East, Dexter, MI 48130, USA
* Author to whom correspondence should be addressed.
Received: 19 April 2013; in revised form: 24 May 2013 / Accepted: 5 June 2013 / Published: 24 June 2013
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.
Keywords: copper-free click; oligonucleotide conjugation; bicyclononyne; azide; strain-promoted cycloaddition
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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.