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

DOI

10.1039/C5CC02728D

Link to Publisher's Edition

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

ISSN (print)

13597345

ISSN (electronic)

1364548X

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