Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-60044

Neef, A B; Luedtke, N W (2011). Dynamic metabolic labeling of DNA in vivo with arabinosyl nucleosides. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 108(51):20404-20409.

[img]Published Version
PDF - Registered users only
View at publisher


Commonly used metabolic labels for DNA, including 5-ethynyl-2′-deoxyuridine (EdU) and BrdU, are toxic antimetabolites that cause DNA instability, necrosis, and cell-cycle arrest. In addition to perturbing biological function, these properties can prevent metabolic labeling studies where subsequent tissue survival is needed. To bypass the metabolic pathways responsible for toxicity, while maintaining the ability to be metabolically incorporated into DNA, we synthesized and evaluated a small family of arabinofuranosyl-ethynyluracil derivatives. Among these, (2′S)-2′-deoxy-2′-fluoro-5-ethynyluridine (F-ara-EdU) exhibited selective DNA labeling, yet had a minimal impact on genome function in diverse tissue types. Metabolic incorporation of F-ara-EdU into DNA was readily detectable using copper(I)-catalyzed azide–alkyne “click” reactions with fluorescent azides. F-ara-EdU is less toxic than both BrdU and EdU, and it can be detected with greater sensitivity in experiments where long-term cell survival and/or deep-tissue imaging are desired. In contrast to previously reported 2′-arabino modified nucleosides and EdU, F-ara-EdU causes little or no cellular arrest or DNA synthesis inhibition. F-ara-EdU is therefore ideally suited for pulse-chase experiments aimed at “birth dating” DNA in vivo. As a demonstration, Zebrafish embryos were microinjected with F-ara-EdU at the one-cell stage and chased by BrdU at 10 h after fertilization. Following 3 d of development, complex patterns of quiescent/senescent cells containing only F-ara-EdU were observed in larvae along the dorsal side of the notochord and epithelia. Arabinosyl nucleoside derivatives therefore provide unique and effective means to introduce bioorthogonal functional groups into DNA for diverse applications in basic research, biotechnology, and drug discovery.


37 citations in Web of Science®
45 citations in Scopus®
Google Scholar™



2 downloads since deposited on 15 Mar 2012
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Deposited On:15 Mar 2012 08:44
Last Modified:05 Apr 2016 15:40
Publisher:National Academy of Sciences
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1073/pnas.1101126108

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page