title: Photo-Tethers for the (Multi-)Cyclic, Conformational Caging of Long Oligonucleotides.
abstract: Intramolecular circularization of DNA oligonucleotides was accomplished by incorporation of alkyne-modified photolabile nucleosides into DNA sequences, followed by a CuI-catalyzed alkyne-azide cycloaddition with bis-azido linker molecules. We determined a range of ring sizes, in which the caged circular oligonucleotides exhibit superior duplex destabilizing properties. Specific binding of a full-length 90 nt C10 aptamer recognizing human Burkitt's lymphoma cells was then temporarily inhibited by locking the aptamer in a bicircularized structure. Irradiation restored the native aptamer conformation resulting in efficient cell binding and uptake. The photo-tether strategy presented here provides a robust and versatile tool for the light-activation of longer functional oligonucleotides, noteworthy without prior knowledge on the structure and the importance of specific nucleotides within a DNA aptamer.
authors.affiliation: Goethe University Frankfurt, Institute for Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Seyfried
authors.affiliation: Life and Medical Science Institute, University of Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Eiden
authors.affiliation: Goethe University Frankfurt, Institute for Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Grebenovsky
authors.affiliation: Life and Medical Science Institute, University of Bonn, Gerhard-Domagk-Str. 1, 53121, Bonn, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Mayer
authors.affiliation: Goethe University Frankfurt, Institute for Organic Chemistry and Chemical Biology, Buchmann Institute for Molecular Life Sciences, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany.
authors.forename: Alexander
authors.identifier: 0000-0003-3541-4548
authors.initials: A
authors.lastname: Heckel
mesh_terms: D002236:Carbohydrate Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D055668:Photochemical Processes
chemical_list: D009841:Oligonucleotides
keywords: DNA; aptamers; click chemistry; cyclization; photochemistry