Print Email Facebook Twitter Intercalating Electron Dyes for TEM Visualization of DNA at the Single-Molecule Level Title Intercalating Electron Dyes for TEM Visualization of DNA at the Single-Molecule Level Author Kabiri, Y. (TU Delft BN/Cees Dekker Lab; Kavli institute of nanoscience Delft) Angelin, Alessandro (Karlsruhe Institut für Technologie) Ahmed, Ishtiaq (Karlsruhe Institut für Technologie) Mutlu, Hatice (Karlsruhe Institut für Technologie) Bauer, Jens (Karlsruhe Institut für Technologie) Niemeyer, Christof M. (Karlsruhe Institut für Technologie) Zandbergen, H.W. (TU Delft QN/Zandbergen Lab; Kavli institute of nanoscience Delft) Dekker, C. (TU Delft BN/Cees Dekker Lab; Kavli institute of nanoscience Delft) Date 2019 Abstract Staining compounds containing heavy elements (electron dyes) can facilitate the visualization of DNA and related biomolecules by using TEM. However, research into the synthesis and utilization of alternative electron dyes has been limited. Here, we report the synthesis of a novel DNA intercalator molecule, bis-acridine uranyl (BAU). NMR spectroscopy and MS confirmed the validity of the synthetic strategy and gel electrophoresis verified the binding of BAU to DNA. For TEM imaging of DNA, two-dimensional DNA origami nanostructures were used as a robust microscopy test object. By using scanning transmission electron microscopy (STEM) imaging, which is favored over conventional wide-field TEM for improved contrast, and therefore, quantitative image analysis, it is found that the synthesized BAU intercalator can render DNA visible, even at the single-molecule scale. For comparison, other staining compounds with a purported affinity towards DNA, such as dichloroplatinum, cisplatin, osmium tetroxide, and uranyl acetate, have been evaluated. The STEM contrast is discussed in terms of the DNA–dye association constants, number of dye molecules bound per base pair, and the electron-scattering capacity of the metal-containing ligands. These findings pave the way for the future development of electron dyes with specific DNA-binding motifs for high-resolution TEM imaging. Subject contrast agentsDNAintercalationscanning transmission electron microscopysingle-molecule studies To reference this document use: http://resolver.tudelft.nl/uuid:5b4a2a42-614c-4517-81d8-c7dd01830683 DOI https://doi.org/10.1002/cbic.201800638 ISSN 1439-4227 Source ChemBioChem: a European journal of chemical biology, 20 (6), 822-830 Part of collection Institutional Repository Document type journal article Rights © 2019 Y. Kabiri, Alessandro Angelin, Ishtiaq Ahmed, Hatice Mutlu, Jens Bauer, Christof M. Niemeyer, H.W. Zandbergen, C. Dekker Files PDF Kabiri_et_al_2019_ChemBioChem.pdf 4.19 MB Close viewer /islandora/object/uuid:5b4a2a42-614c-4517-81d8-c7dd01830683/datastream/OBJ/view