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

页码：11178 / 11181

页数：4

共 33 条

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