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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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Supplementary files

Article information


Submitted
04 Dec 2017
Accepted
02 Jan 2018
First published
17 Jan 2018

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2018,9, 1860-1866
Article type
Edge Article

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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