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

Zhangfeng Zhong, Li Juan Liu, Zhi Qiang Dong, Lihua Lu, Modi Wang, Chung Hang Leung*, Edmond Dik Lung MA, Yitao Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11178-11181
Number of pages4
JournalChemical Communications
Volume51
Issue number56
DOIs
Publication statusPublished - 18 Jul 2015

Scopus Subject Areas

  • Catalysis
  • Electronic, Optical and Magnetic Materials
  • Ceramics and Composites
  • Chemistry(all)
  • Surfaces, Coatings and Films
  • Metals and Alloys
  • Materials Chemistry

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