Diselenolane-mediated Cellular Uptake

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2018 Apr 21

PMID 29675232

Citations 16

Authors

Nicolas Chuard

Amalia I Poblador-Bahamonde

Lili Zong

Eline Bartolami

Jana Hildebrandt

Wolfgang Weigand

Naomi Sakai

Stefan Matile

Affiliations

Soon will be listed here.

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.

Citing Articles

Inclusive Pattern Generation Protocols to Decode Thiol-Mediated Uptake.

Saidjalolov S, Coelho F, Mercier V, Moreau D, Matile S ACS Cent Sci. 2024; 10(5):1033-1043.

PMID: 38799667 PMC: 11117725. DOI: 10.1021/acscentsci.3c01601.

Fluorescent Probes for Mammalian Thioredoxin Reductase: Mechanistic Analysis, Construction Strategies, and Future Perspectives.

Song Z, Fan C, Zhao J, Wang L, Duan D, Shen T Biosensors (Basel). 2023; 13(8).

PMID: 37622897 PMC: 10452626. DOI: 10.3390/bios13080811.

Cyclic Thiosulfonates for Thiol-Mediated Uptake: Cascade Exchangers, Transporters, Inhibitors.

Kato T, Lim B, Cheng Y, Pham A, Maynard J, Moreau D JACS Au. 2022; 2(4):839-852.

PMID: 35557769 PMC: 9088311. DOI: 10.1021/jacsau.1c00573.

An Orthogonal Dynamic Covalent Chemistry Tool for Ring-Opening Polymerization of Cyclic Oligochalcogenides on Detachable Helical Peptide Templates.

Laurent Q, Sakai N, Matile S Chemistry. 2022; 28(33):e202200785.

PMID: 35416345 PMC: 9324982. DOI: 10.1002/chem.202200785.

Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically.

Felber J, Poczka L, Scholzen K, Zeisel L, Maier M, Busker S Nat Commun. 2022; 13(1):1754.

PMID: 35365603 PMC: 8975869. DOI: 10.1038/s41467-022-29136-4.

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