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Chemoselective Modification of Vinyl DNA by Triazolinediones
Author(s) -
Naik Anu,
Alzeer Jawad,
Triemer Therese,
Bujalska Anna,
Luedtke Nathan W.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201702554
Subject(s) - bioconjugation , nucleobase , nucleic acid , alkene , chemistry , oligonucleotide , combinatorial chemistry , dna , context (archaeology) , cycloaddition , catalysis , organic chemistry , biology , biochemistry , paleontology
A new method for the post‐synthetic modification of nucleic acids was developed that involves mixing a phenyl triazolinedione (PTAD) derivative with DNA containing a vinyl nucleobase. The resulting reactions proceeded through step‐wise mechanisms, giving either a formal [4+2] cycloaddition product, or, depending on the context of nucleobase, PTAD addition along with solvent trapping to give a secondary alcohol in water. Catalyst‐free addition between PTAD and the terminal alkene of 5‐vinyl‐2′‐deoxyuridine (VdU) was exceptionally fast, with a second‐order rate constant of 2×10 3 m −1 s −1 . PTAD derivatives selectively reacted with VdU‐containing oligonucleotides in a conformation‐selective manner, with higher yields observed for G‐quadruplex versus duplex DNA. These results demonstrate a new strategy for copper‐free bioconjugation of DNA that can potentially be used to probe nucleic acid conformations in cells.