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.

中文翻译：

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微管溶素（一种来自粘细菌的抗有丝分裂肽）的作用机理。

Tubulysin A是具有抗有丝分裂活性的高度细胞毒性肽，可诱导细胞微管耗竭并触发凋亡过程。处理过的细胞在G2 / M期积累。Tubulysin A比长春花碱更有效地抑制微管蛋白聚合，并诱导分离的微管制剂解聚。在无细胞系统或细胞系中，都无法通过与埃博霉素B和紫杉醇进行预温育来防止微管解聚。在竞争实验中，微管溶素A以非竞争性方式强烈干扰长春碱与微管蛋白的结合。表观Ki为3 microM。电子显微镜研究表明，微管溶素A诱导了环，双环和风车结构的形成。微管蛋白溶酶A的作用方式类似于肽抗有丝分裂剂dolastatin 10，视紫红质素A和半乳糖素的作用方式。正在努力开发这一新类化合物作为抗癌药。