The C29-C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags
The C29-C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags
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抗肿瘤大环内酯 aplyronine A 的 C29-C34 部分可作为多功能肌动蛋白亲和标签
DOI：
10.1039/d1cc04259a
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发表时间：
2021
影响因子：
4.9
通讯作者：
Kita Masaki
中科院分区：
文献类型：
--
作者：
Utomo Didik Huswo;Fujieda Akari;Tanaka Kentaro;Takahashi Momoko;Futaki Kentaro;Tanabe Kenta;Kigoshi Hideo;Kita Masaki
基于蛋白质-蛋白质相互作用（PPI）的天然产物的抗癌药物开发是一种有前途的策略。我们开发了一种抗肿瘤的海洋大环内酯类化合物-阿克罗宁A（阿帕）的结构简化的C29-C34侧链类似物。其中，具有C_（23）酰氧基的类似物、C_（29）N，N-二甲基-L-丙氨酸酯和C_（34）N-亚甲基酰胺表现出较强的肌动蛋白解聚活性。结合动力学，分子对接，亲和纯化实验表明，他们是多才多艺的肌动蛋白亲和标签，以加快研究的细胞骨架动力学和PPI为基础的药物线索的发展有关的行动模式。
Anticancer drug development inspired by natural products based on protein–protein interactions (PPI) is a promising strategy. We developed structurally-simplified C29–C34 side-chain analogs of aplyronine A (ApA), an antitumor marine macrolide. Among them, the analog possessing the C23 acyloxy group, the C29 N,N-dimethyl-L-alanine ester and the C34 N-methyl enamide showed potent actin-depolymerizing activity. Binding kinetics, molecular docking, and affinity-purification experiments revealed that they are versatile actin-affinity tags to accelerate studies on the mode of action related to cytoskeletal dynamics and the development of PPI-based drug leads.