Premium
Photo‐Tethers for the (Multi‐)Cyclic, Conformational Caging of Long Oligonucleotides
Author(s) -
Seyfried Patrick,
Eiden Laura,
Grebenovsky Nikolai,
Mayer Günter,
Heckel Alexander
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201610025
Subject(s) - aptamer , oligonucleotide , chemistry , linker , dna , biophysics , duplex (building) , nucleotide , cycloaddition , intramolecular force , combinatorial chemistry , small molecule , azide , stereochemistry , biochemistry , microbiology and biotechnology , biology , catalysis , organic chemistry , computer science , gene , operating system
Intramolecular circularization of DNA oligonucleotides was accomplished by incorporation of alkyne‐modified photolabile nucleosides into DNA sequences, followed by a Cu I ‐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.