Mechanism of Action of Tubulysin, an Antimitotic Peptide from Myxobacteria
| Autor: | Yasser A. Elnakady, Hans Reichenbach, Mohamed W. Khalil, Heinrich Lünsdorf, Florenz Sasse |
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| Rok vydání: | 2006 |
| Předmět: |
Time Factors
Cell Molecular Conformation Antineoplastic Agents Peptide Biology Binding Competitive Sensitivity and Specificity Biochemistry Structure-Activity Relationship chemistry.chemical_compound Microtubule medicine Humans Structure–activity relationship Myxococcales Molecular Biology Cells Cultured chemistry.chemical_classification Binding Sites Cell Cycle Organic Chemistry Vinblastine Microscopy Electron medicine.anatomical_structure Tubulin Mechanism of action chemistry Paclitaxel biology.protein Molecular Medicine Drug Screening Assays Antitumor medicine.symptom Oligopeptides medicine.drug |
| Zdroj: | ChemBioChem. 7:678-683 |
| ISSN: | 1439-4227 |
| DOI: | 10.1002/cbic.200500421 |
| Popis: | Tubulysin A is a highly cytotoxic peptide with antimitotic activity that induces depletion of cell microtubules and triggers the apoptotic process. Treated cells accumulated in the G2/M phase. Tubulysin A inhibited tubulin polymerization more efficiently than vinblastine and induced depolymerization of isolated microtubule preparations. Microtubule depolymerization could not be prevented by preincubation with epothilone B and paclitaxel, neither in cell-free systems nor in cell lines. In competition experiments, tubulysin A strongly interfered with the binding of vinblastine to tubulin in a noncompetitive way; the apparent Ki was 3 microM. Electron microscopy investigations showed that tubulysin A induced the formation of rings, double rings, and pinwheel structures. The mode of action of tubulysin A resembled that of peptide antimitotics dolastatin 10, phomopsin A, and hemiasterlin. Efforts are underway to develop this new group of compounds as anticancer drugs. |
| Databáze: | OpenAIRE |
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