Department of Chemistry
Structure-based discovery of an immunomodulatory inhibitor of TLR1–TLR2 heterodimerization from a natural product-like database
© The Royal Society of Chemistry 2015. 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-α and IL-6 secretion in Pam3CSK4-induced macrophages. Moreover, compound 1 inhibited the phagocytic activity of macrophages, presumably through modulation of TLR1-TLR2 signaling and inactivation of NF-κB. 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.
Source Publication Title
Royal Society of Chemistry
Zhong, Zhangfeng, Li-Juan Liu, Zhi-Qiang Dong, Lihua Lu, Modi Wang, Chung-Hang Leung, Dik-Lung Ma, and Yitao Wang. "Structure-based discovery of an immunomodulatory inhibitor of TLR1–TLR2 heterodimerization from a natural product-like database." Chemical Communications 51.56 (2015): 11178-11181.