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Chemoselective Modification of Vinyl DNA by Triazolinediones


Naik, Anu; Alzeer, Jawad; Triemer, Therese; Bujalska, Anna; Luedtke, Nathan W (2017). Chemoselective Modification of Vinyl DNA by Triazolinediones. Angewandte Chemie, 129(36):10990-10993.

Abstract

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 2×103  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.

Abstract

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 2×103  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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Uncontrolled Keywords:General Medicine
Language:English
Date:2017
Deposited On:12 Jun 2018 13:09
Last Modified:13 Mar 2019 11:21
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1521-3757
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/ange.201702554
PubMed ID:28561928
Project Information:
  • : FunderSNSF
  • : Grant ID205320_165949
  • : Project TitleLive-cell imaging of DNA conformation and metabolism

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