Programmable DNA interstrand crosslinking by alkene-alkyne [2+2] photocycloaddition
Please always quote using this URN: urn:nbn:de:bvb:20-opus-311822
- Covalent crosslinking of DNA strands provides a useful tool for medical, biochemical and DNA nanotechnology applications. Here we present a light-induced interstrand DNA crosslinking reaction using the modified nucleoside 5-phenylethynyl-2’-deoxyuridine (\(^{Phe}\)dU). The crosslinking ability of \(^{Phe}\)dU was programmed by base pairing and by metal ion interaction at the Watson-Crick base pairing site. Rotation to intrahelical positions was favored by hydrophobic stacking and enabled an unexpected photochemical alkene-alkyne [2+2]Covalent crosslinking of DNA strands provides a useful tool for medical, biochemical and DNA nanotechnology applications. Here we present a light-induced interstrand DNA crosslinking reaction using the modified nucleoside 5-phenylethynyl-2’-deoxyuridine (\(^{Phe}\)dU). The crosslinking ability of \(^{Phe}\)dU was programmed by base pairing and by metal ion interaction at the Watson-Crick base pairing site. Rotation to intrahelical positions was favored by hydrophobic stacking and enabled an unexpected photochemical alkene-alkyne [2+2] cycloaddition within the DNA duplex, resulting in efficient formation of a \(^{Phe}\)dU-dimer after short irradiation times of a few seconds. A \(^{Phe}\)dU dimer-containing DNA was shown to efficiently bind a helicase complex, but the covalent crosslink completely prevented DNA unwinding, suggesting possible applications in biochemistry or structural biology.…
Author: | Hermann NeitzORCiD, Irene BessiORCiD, Jochen KuperORCiD, Caroline KiskerORCiD, Claudia HöbartnerORCiD |
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URN: | urn:nbn:de:bvb:20-opus-311822 |
Document Type: | Preprint |
Faculties: | Fakultät für Biologie / Rudolf-Virchow-Zentrum |
Fakultät für Chemie und Pharmazie / Institut für Organische Chemie | |
Language: | English |
Parent Title (English): | Journal of the American Chemical Society |
Year of Completion: | 2023 |
Edition: | submitted version |
Source: | Journal of the American Chemical Society (2023), https://doi.org/10.1021/jacs.3c01611 |
DOI: | https://doi.org/10.1021/jacs.3c01611 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
Tag: | DNA-based nanostructures; DNA-processing enzymes; alkene-alkyne [2+2] photocycloaddition; light-induced interstrand DNA crosslinking |
Release Date: | 2023/04/21 |
EU-Project number / Contract (GA) number: | 682586 |
OpenAIRE: | OpenAIRE |
Note: | This document is the unedited Author's version of a Submitted Work that was subsequently accepted for publication in Journal of the American Chemical Society, copyright © 2023 The Authors. Published by American Chemical Society. after peer review. To access the final edited and published work see https://doi.org/10.1021/jacs.3c01611. |
Licence (German): | Deutsches Urheberrecht |