Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1016/j.jconrel.2015.04.037 |
| Title (Primary) | A cleavable cytolysin–neuropeptide Y bioconjugate enables specific drug delivery and demonstrates intracellular mode of action |
| Author | Ahrens, V.M.; Kostelnik, K.B.; Rennert, R.; Böhme, D.; Kalkhof, S.; Kosel, D.; Weber, L.; von Bergen, M.; Beck-Sickinger, A.G. |
| Source Titel | Journal of Controlled Release |
| Year | 2015 |
| Department | PROTEOM |
| Volume | 209 |
| Page From | 170 |
| Page To | 178 |
| Language | englisch |
| Keywords | Peptide–drug conjugate; Neuropeptide Y; Cytolysin; Breast cancer; SILAC; Quantitative proteomics |
| UFZ wide themes | RU3; |
| Abstract | Myxobacterial tubulysins are promising chemotherapeutics inhibiting microtubule polymerization, however, high unspecific toxicity so far prevents their application in therapy. For selective cancer cell targeting, here the coupling of a synthetic cytolysin to the hY1-receptor preferring peptide [F7,P34]-neuropeptide Y (NPY) using a labile disulfide linker is described. Since hY1-receptors are overexpressed in breast tumors and internalize rapidly, this system has high potential as peptide–drug shuttle system. Molecular characterization of the cytolysin–[F7,P34]-NPY bioconjugate revealed potent receptor activation and receptor-selective internalization, while viability studies verified toxicity. Triple SILAC studies comparing free cytolysin with the bioconjugate demonstrated an intracellular mechanism of action regardless of the delivery pathway. Treatments resulted in a regulation of proteins implemented in cell cycle arrest confirming the tubulysin-like effect of the cytolysin. Thus, the cytolysin–peptide bioconjugate fused by a cleavable linker enables a receptor-specific delivery as well as a potent intracellular drug-release with high cytotoxic activity. |
| Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=16149 |
| Ahrens, V.M., Kostelnik, K.B., Rennert, R., Böhme, D., Kalkhof, S., Kosel, D., Weber, L., von Bergen, M., Beck-Sickinger, A.G. (2015): A cleavable cytolysin–neuropeptide Y bioconjugate enables specific drug delivery and demonstrates intracellular mode of action J. Control. Release 209 , 170 - 178 10.1016/j.jconrel.2015.04.037 |
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