2. Academic Validation
  3. Design, synthesis, and evaluation of a novel macrocyclic anti-EV71 agent

Design, synthesis, and evaluation of a novel macrocyclic anti-EV71 agent

  • Bioorg Med Chem. 2020 Jun 15;28(12):115551. doi: 10.1016/j.bmc.2020.115551.
Peng Li 1,  Siqi Wu 2,  Tianyichen Xiao 2,  Yunlong Li 2,  Zhiming Su 2,  Wei Wei 3,  Fei Hao 3,  Guoping Hu 3,  Fusen Lin 3,  Xinsheng Chen 3,  Zhengxian Gu 3,  Tianwei Lin 4,  Haiying He 3,  Jian Li 5,  Shuhui Chen 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Cancer Research Center of Xiamen University, Xiamen, Fujian, China; State Key Laboratory of Drug Lead Compound Research, WuXi AppTec (Shanghai) Co., Ltd., Shanghai, China.
  • 2 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Cancer Research Center of Xiamen University, Xiamen, Fujian, China.
  • 3 State Key Laboratory of Drug Lead Compound Research, WuXi AppTec (Shanghai) Co., Ltd., Shanghai, China.
  • 4 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China; Cancer Research Center of Xiamen University, Xiamen, Fujian, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Drug Lead Compound Research, WuXi AppTec (Shanghai) Co., Ltd., Shanghai, China. Electronic address: [email protected].
PMID: 32503695 DOI: 10.1016/j.bmc.2020.115551
Abstract

We describe here the design, synthesis, and evaluation of a macrocyclic peptidomimetic as a potent agent targeting Enterovirus A71 (EV71). The compound has a 15-membered macrocyclic ring in a defined conformation. Yamaguchi esterification reaction was used to close the 15-membered macrocycle instead of the typical Ru-catalyzed ring-closing olefin metathesis reaction. The crystallographic characterization of the complex between this compound and its target, 3C protease from EV71, validated the design and paved the way for the generation of a new series of anti-EV71 agents.

Keywords

3C Protease Inhibitor; Enterovirus 71; Macrocycles; X-ray crystallography.

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