Diselenolane-Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein-Coated Quantum Dots

Eline Bartolami, Dimitris Basagiannis, Lili Zong, Rémi Martinent, Yasunori Okamoto, Quentin Laurent, Thomas R. Ward, Marcos Gonzalez-Gaitan, Naomi Sakai, Stefan Matile

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Cyclic oligochalcogenides are emerging as powerful tools to penetrate cells. With disulfide ring tension maximized, selenium chemistry had to be explored next to enhance speed and selectivity of dynamic covalent exchange on the way into the cytosol. We show that diseleno lipoic acid (DiSeL) delivers a variety of relevant substrates. DiSeL-driven uptake of artificial metalloenzymes enables bioorthogonal fluorophore uncaging within cells. Binding of a bicyclic peptide, phalloidin, to actin fibers evinces targeted delivery to the cytosol. Automated tracking of diffusive compared to directed motility and immobility localizes 79 % of protein-coated quantum dots (QDs) in the cytosol, with little endosomal capture (0.06 %). These results suggest that diselenolanes might act as molecular walkers along disulfide tracks in locally denatured membrane proteins, surrounded by adaptive micellar membrane defects. Miniscule and versatile, DiSeL tags are also readily available, stable, soluble, and non-toxic.

Original languageEnglish
Pages (from-to)4047-4051
Number of pages5
JournalChemistry - A European Journal
Volume25
Issue number16
DOIs
Publication statusPublished - 2019 Mar 15

Keywords

  • biotechnology
  • diselenolane
  • protein delivery
  • ring tension
  • streptavidin

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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