title: 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.
authors.affiliation: Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. jawanup@yahoo.com
authors.forename: Anup M
authors.initials: AM
authors.lastname: Jawalekar
authors.forename: Sudip
authors.initials: S
authors.lastname: Malik
authors.forename: Jorge M M
authors.initials: JM
authors.lastname: Verkade
authors.forename: Brian
authors.initials: B
authors.lastname: Gibson
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Barta
authors.forename: John C
authors.initials: JC
authors.lastname: Hodges
authors.forename: Alan
authors.initials: A
authors.lastname: Rowan
authors.forename: Floris L
authors.initials: FL
authors.lastname: van Delft
mesh_terms: D001386:Azides / Q000737:chemistry; D002384:Catalysis; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry*; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001386:Azides; D009841:Oligonucleotides; D003300:Copper