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Diselenolane-mediated cellular uptake

Publié dansChemical Science, vol. 9, no. 7, p. 1860-1866
Date de publication2018
Résumé

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.

Groupe de recherche
Citation (format ISO)
CHUARD, Nicolas et al. Diselenolane-mediated cellular uptake. In: Chemical Science, 2018, vol. 9, n° 7, p. 1860–1866. doi: 10.1039/C7SC05151D
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Article (Published version)
Identifiants
ISSN du journal2041-6520
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Création15/02/2018 09:18:00
Première validation15/02/2018 09:18:00
Heure de mise à jour15/03/2023 07:52:55
Changement de statut15/03/2023 07:52:55
Dernière indexation12/02/2024 12:49:35
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