http://dx.doi.org/10.1039/C5CC02728D">
 

Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

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

Language

English

Abstract

© 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.

Publication Date

2015

Source Publication Title

Chemical Communications

Volume

51

Issue

56

Start Page

11178

End Page

11181

Publisher

Royal Society of Chemistry

ISSN (print)

13597345

ISSN (electronic)

1364548X

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