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Issue 7, 2018
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Diselenolane-mediated cellular uptake

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Abstract

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.

Graphical abstract: Diselenolane-mediated cellular uptake

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Publication details

The article was received on 04 Dec 2017, accepted on 02 Jan 2018 and first published on 17 Jan 2018


Article type: Edge Article
DOI: 10.1039/C7SC05151D
Chem. Sci., 2018,9, 1860-1866
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Diselenolane-mediated cellular uptake

    N. Chuard, A. I. Poblador-Bahamonde, L. Zong, E. Bartolami, J. Hildebrandt, W. Weigand, N. Sakai and S. Matile, Chem. Sci., 2018, 9, 1860
    DOI: 10.1039/C7SC05151D

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