FEBS Letters | |
Structural insights into the design of indole derivatives as tubulin polymerization inhibitors | |
article | |
Yuanyuan Li1  Jiazhen Yang1  Lu Niu1  Daojun Hu1  Huijuan Li1  Lijuan Chen1  Yamei Yu1  Qiang Chen1  | |
[1] Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy | |
关键词: colchicine binding site; D64131; drug design; indole; tubulin; | |
DOI : 10.1002/1873-3468.13566 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Microtubules are composed of ab-tubulin heterodimers, and drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Small synthetic molecules with an indole nucleus as a core structure have been identified as microtubule inhibitors and recognized as anticancer agents. However, structural information for the interactions between indole derivatives and tubulin is sparse. Here, we present the 2.55 A crystal structure of tubulin in complex with the indole derivative D64131. We compare the binding modes of D64131, colchicine, and five other indole derivatives to tubulin. These results reveal the interactions between the indole derivatives and tubulin, explain previous results of structure-activity-relationship (SAR) studies and, thus, provide insights into the development of new indole derivatives targeting the colchicine binding site.
【 授权许可】
Unknown
【 预 览 】
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