Cellular Uptake of Substrate-Initiated Cell-Penetrating Poly(disulfide)s
| Autor: | Giulio Gasparini, Naomi Sakai, Stefan Matile, David V. Tulumello, Guillaume Molinard, Shana O. Kelley, Sandra Ward, Aurélien Roux, Eun Kyoung Bang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Endosome
Cell-Penetrating Peptides 010402 general chemistry Branching (polymer chemistry) Endocytosis 01 natural sciences Biochemistry Catalysis Polymerization HeLa Colloid and Surface Chemistry Humans Disulfides Sulfhydryl Compounds biology 010405 organic chemistry Chemistry Cell Membrane Transporter General Chemistry biology.organism_classification 0104 chemical sciences Cytosol Covalent bond ddc:540 HeLa Cells |
| Zdroj: | Journal of the American Chemical Society, Vol. 136, No 16 (2014) pp. 6069-6074 J. Am. Chem. Soc. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY |
| ISSN: | 0002-7863 |
| Popis: | Substrate-initiated, self-inactivating, cell-penetrating poly(disulfide)s (siCPDs) are introduced as general transporters for the covalent delivery of unmodified substrates of free choice. With ring-opening disulfide-exchange polymerization, we show that guanidinium-rich siCPDs grow on fluorescent substrates within minutes under the mildest conditions. The most active siCPD transporters reach the cytosol of HeLa cells within 5 min and depolymerize in less than 1 min to release the native substrate. Depolymerized right after use, the best siCPDs are nontoxic under conditions where cell-penetrating peptides (CPPs) are cytotoxic. Intracellular localization (cytosol, nucleoli, endosomes) is independent of the substrate and can be varied on demand, through choice of polymer composition. Insensitivity to endocytosis inhibitors and classical structural variations (hydrophobicity, aromaticity, branching, boronic acids) suggest that the best siCPDs act differently. Supported by experimental evidence, a unique combination of the counterion-mediated translocation of CPPs with the underexplored, thiol-mediated covalent translocation is considered to account for this decisive difference. |
| Databáze: | OpenAIRE |
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