Strained Cyclic Disulfides Enable Cellular Uptake by Reacting with the Transferrin Receptor
| Autor: | Daniel Abegg, Giulio Gasparini, Alexander Adibekian, Dominic Gregor Hoch, Stefan Matile, Anton Shuster, Eline Bartolami |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Settore MED/29 - CHIRURGIA MAXILLOFACCIALE
Endocytic cycle Transferrin receptor Apoptosis Thiophenes 010402 general chemistry Proteomics 01 natural sciences Biochemistry Catalysis Dose-Response Relationship Residue (chemistry) chemistry.chemical_compound Structure-Activity Relationship Colloid and Surface Chemistry Drug Delivery Systems Receptors Transferrin Receptors Humans Disulfides chemistry.chemical_classification Binding Sites Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Transferrin General Chemistry 0104 chemical sciences Covalent bond ddc:540 Asparagusic acid Drug Intracellular HeLa Cells |
| Zdroj: | Journal of the American Chemical Society, Vol. 139, No 1 (2017) pp. 231-238 |
| ISSN: | 0002-7863 |
| Popis: | In this study, we demonstrate that appendage of a single asparagusic acid residue (AspA tag) is sufficient to ensure efficient cellular uptake and intracellular distribution of fully unprotected peptides. We apply this new delivery method to induce apoptotic response in cancer cells using long (up to 20mer) BH3 domain peptides. Moreover, to understand the molecular mechanism of the cellular uptake, we perform chemical proteomics experiments and identify the direct molecular targets of the asparagusic acid tag. Our findings document covalent bond formation between the asparagusic acid moiety and the cysteines 556 and 558 on the surface of the transferrin receptor resulting in subsequent endocytic uptake of the payload. We believe that the small size, low cellular toxicity and the efficient transferrin receptor-mediated uptake render the AspA tag highly attractive for various life science applications. |
| Databáze: | OpenAIRE |
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