Graduate School of Pure and Applied Sciences, University of Tsukuba, Japan.
Nat Prod Rep. 2015 Apr;32(4):534-42. doi: 10.1039/c4np00129j.
Various marine natural products that target cytoskeletal proteins have been discovered. A few of these compounds have recently been shown to induce or inhibit protein-protein interactions. Lobophorolide, an actin filament-disrupting macrolide, binds to actin with a unique 2 : 2 stoichiometry in which two lobophorolide molecules cooperate to stabilize an actin dimer. Adociasulfates, merotriterpenoid derivatives, inhibit microtubule-stimulated ATPase activity of a motor protein kinesin by blocking both the binding of microtubules and the processive motion of kinesin along microtubules. The antitumor macrolide aplyronine A synergistically binds to tubulin in association with actin, and prevents spindle formation and mitosis. In this highlight, we address recent chemical biology studies on these mechanistically-attractive marine natural products. These findings may be useful for the design and development of new pharmacological tools and therapeutic agents.
已经发现了许多靶向细胞骨架蛋白的海洋天然产物。最近有一些研究表明，这些化合物可以诱导或抑制蛋白质-蛋白质相互作用。破坏微丝的大环内酯类化合物 lobophorolide 与肌动蛋白以独特的 2:2 化学计量比结合，其中两个 lobophorolide 分子协同作用稳定肌动蛋白二聚体。Adociasulfates 是 merotriterpenoid 衍生物，通过阻止微管结合和 kinesin 在微管上的连续运动来抑制微管刺激的动力蛋白 kinesin 的 ATP 酶活性。抗肿瘤大环内酯类化合物 aplyronine A 与肌动蛋白协同结合微管，并防止纺锤体形成和有丝分裂。在这篇重点介绍中，我们讨论了这些具有吸引力的海洋天然产物的最新化学生物学研究。这些发现可能有助于设计和开发新的药理学工具和治疗剂。
