Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database

被引：52
|
作者：
Zhong, Zhangfeng [1 ]
Liu, Li-Juan [1 ]
Dong, Zhi-Qiang [1 ]
Lu, Lihua [2 ]
Wang, Modi [2 ]
Leung, Chung-Hang [1 ]
Ma, Dik-Lung [2 ]
Wang, Yitao [1 ]
机构：
[1] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
[2] Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China
来源：
CHEMICAL COMMUNICATIONS | 2015年 / 51卷 / 56期
关键词：
TOLL-LIKE RECEPTORS; INNATE IMMUNE-RESPONSES; INCREASES PHAGOCYTOSIS; MICROGLIAL CELLS; TLR2; RECOGNITION;
D O I：
10.1039/c5cc02728d
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
We report herein the identification of an immunomodulatory natural product-like compound 1 as a direct inhibitor of TLR1-TLR2 heterodimerization. Compound 1 suppressed TNF-alpha and IL-6 secretion in Pam(3)CSK(4)-induced macrophages. Moreover, compound 1 inhibited the phagocytic activity of macrophages, presumably through modulation of TLR1-TLR2 signaling and inactivation of NF-kappa B. Molecular docking revealed that compound 1 bound to the interface region of TLR1-TLR2 by forming two hydrogen bonds with residues lining the binding site. To our knowledge, compound 1 has been only the second inhibitor overall of TLR1-TLR2 heterodimerization reported to date.
引用
收藏
页码：11178 / 11181
页数：4
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