TY - JOUR A1 - Neitz, Hermann A1 - Bessi, Irene A1 - Kachler, Valentin A1 - Michel, Manuela A1 - Höbartner, Claudia T1 - Tailored tolane‐perfluorotolane assembly as supramolecular base pair replacement in DNA JF - Angewandte Chemie International Edition N2 - Arene‐fluoroarene interactions offer outstanding possibilities for engineering of supramolecular systems, including nucleic acids. Here, we implement the tolane‐perfluorotolane interaction as base pair replacement in DNA. Tolane (THH) and perfluorotolane (TFF) moieties were connected to acyclic backbone units, comprising glycol nucleic acid (GNA) or butyl nucleic acid (BuNA) building blocks, that were incorporated via phosphoramidite chemistry at opposite positions in a DNA duplex. Thermodynamic analyses by UV thermal melting revealed a compelling stabilization by THH/TFF heteropairs only when connected to the BuNA backbone, but not with the shorter GNA linker. Detailed NMR studies confirmed the preference of the BuNA backbone for enhanced polar π‐stacking. This work defines how orthogonal supramolecular interactions can be tailored by small constitutional changes in the DNA backbone, and it inspires future studies of arene‐fluoroarene‐programmed assembly of DNA. KW - arene-fluoroarene KW - artificial base pair KW - DNA KW - sSupramolecular interaction KW - XNA Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312575 VL - 62 IS - 1 ER - TY - INPR A1 - Neitz, Hermann A1 - Bessi, Irene A1 - Kuper, Jochen A1 - Kisker, Caroline A1 - Höbartner, Claudia T1 - Programmable DNA interstrand crosslinking by alkene-alkyne [2+2] photocycloaddition T2 - Journal of the American Chemical Society N2 - 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. KW - light-induced interstrand DNA crosslinking KW - alkene-alkyne [2+2] photocycloaddition KW - DNA-based nanostructures KW - DNA-processing enzymes Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311822 N1 - 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. ET - submitted version ER - TY - INPR A1 - Neitz, Hermann A1 - Höbartner, Claudia T1 - A tolane-modified 5-ethynyluridine as a universal and fluorogenic photochemical DNA crosslinker T2 - Chemical Communications N2 - We report the fluorescent nucleoside ToldU and its application as a photoresponsive crosslinker in three different DNA architectures with enhanced fluorescence emission of the crosslinked products. The fluorogenic ToldU crosslinking reaction enables the assembly of DNA polymers in a hybridization chain reaction for the concentration-dependent detectio of a specific DNA sequence. KW - Tolane-Modified Fluorescent Nucleosides KW - Photoresponsive DNA Crosslinker Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328255 ET - submitted version ER - TY - THES A1 - Neitz, Hermann T1 - Hydrophobic recognition motifs in functionalized DNA T1 - Hydrophobe Erkennungsmotive in funktionalisierter DNA N2 - In wässriger Umgebung spielen hydrophobe Wechselwirkungen eine wichtige Rolle für die DNA. Die Einführung von Modifikationen, die auf hydrophoben aromatischen Einheiten basieren, kann die Erkennung und Reaktivität von funktionellen Gruppen in der DNA steuern. Modifikationen können durch ein künstliches Rückgrat oder in Form einer Erweiterung der Nukleobasen eingebracht werden und so zu zusätzlichen Eigenschaften der DNA führen. Diese Dissertation befasst sich mit der Verwendung von hydrophoben Einheiten zur Funktionalisierung von DNA. Im ersten Teil der Arbeit wurde das Tolanmotiv (Diphenylacetylen) in Kombination mit dem acyclischen Rückgrat von GNA und BuNA verwendet, um Erkennungseinheiten im DNA-Kontext zu erzeugen. Die gezielte Fluorierung der aromatischen Ringe des Tolan-Bausteins bildete die Grundlage für eine supramolekulare Sprache, die auf Aren-Fluoroaren-Wechselwirkungen basiert. Die spezifische Erkennung wurde mittels thermodynamischer, kinetischer und NMR-spektroskopischer Methoden untersucht. Im zweiten Teil der Arbeit wurden Desoxyuridin-Derivate mit einer hydrophoben aromatischen Modifikation hergestellt und in die DNA-Doppelhelix eingebaut. Die Bestrahlung mit UV-Licht führte zu einer [2+2]-Cycloaddition zwischen zwei modifizierten Nukleosiden in der DNA. Das Reaktionsprodukt wurde strukturell charakterisiert und die Reaktion in verschiedenen biochemischen und nanotechnologischen DNA-Anwendungen eingesetzt. N2 - In aqueous environment, hydrophobic interactions play an important role for DNA. The introduction of modifications based on hydrophobic aromatic moieties offers additional ways for controlling recognition and reactivity of functional groups in DNA. Modifications are introduced through an artificial backbone or in the form of an extension of the nucleobases, resulting in additional properties of the DNA. This dissertation focuses on the use of hydrophobic units for the functionalization of DNA. In the first part of the work, the tolane (i. e. diphenylacetylene) motif was used in combination with the acyclic backbone of GNA and BuNA to generate recognition units in the DNA context. Fluorination of the aromatic rings in the tolane moiety provided the basis for a supramolecular language based on arene-fluoroarene interactions. The specific recognition was investigated by thermodynamic, kinetic and NMR spectroscopic methods. In the second part of the work, deoxyuridine derivatives with a hydrophobic aromatic modification were prepared and incorporated into DNA duplexes. The irradiation with UV light led to a [2+2] cycloaddition reaction between two modified nucleosides in the DNA. This reaction product was structurally characterized and the reaction was used in various biochemical and nanotechnological DNA applications. KW - Supramolekulare Chemie KW - Arene-Fluoroarene KW - Artificial Base Pair KW - Supramolecular Interaction KW - XNA KW - Crosslinking KW - DNA KW - DNS Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-348382 ER -