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Diselenolane-mediated cellular uptake.
Journal article

Diselenolane-mediated cellular uptake.

  • Chuard N Department of Organic Chemistry , University of Geneva , Geneva , Switzerland . Email: stefan.matile@unige.ch ; http://www.unige.ch/sciences/chiorg/matile/ ; Tel: +41 22 379 6523.
  • Poblador-Bahamonde AI Department of Organic Chemistry , University of Geneva , Geneva , Switzerland . Email: stefan.matile@unige.ch ; http://www.unige.ch/sciences/chiorg/matile/ ; Tel: +41 22 379 6523.
  • Zong L Department of Organic Chemistry , University of Geneva , Geneva , Switzerland . Email: stefan.matile@unige.ch ; http://www.unige.ch/sciences/chiorg/matile/ ; Tel: +41 22 379 6523.
  • Bartolami E Department of Organic Chemistry , University of Geneva , Geneva , Switzerland . Email: stefan.matile@unige.ch ; http://www.unige.ch/sciences/chiorg/matile/ ; Tel: +41 22 379 6523.
  • Hildebrandt J Institute of Inorganic and Analytical Chemistry , Friedrich-Schiller University Jena , Germany.
  • Weigand W Institute of Inorganic and Analytical Chemistry , Friedrich-Schiller University Jena , Germany.
  • Sakai N Department of Organic Chemistry , University of Geneva , Geneva , Switzerland . Email: stefan.matile@unige.ch ; http://www.unige.ch/sciences/chiorg/matile/ ; Tel: +41 22 379 6523.
  • Matile S Department of Organic Chemistry , University of Geneva , Geneva , Switzerland . Email: stefan.matile@unige.ch ; http://www.unige.ch/sciences/chiorg/matile/ ; Tel: +41 22 379 6523.
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  • 2018-04-21
Published in:
  • Chemical science. - 2018
General Chemistry
English The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/103806
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