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

doi:10.1039/c5cc02728d

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

Department of Chemistry

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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 language	English
Pages (from-to)	11178-11181
Number of pages	4
Journal	Chemical Communications
Volume	51
Issue number	56
DOIs	https://doi.org/10.1039/c5cc02728d
Publication status	Published - 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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title = "Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database",

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.",

author = "Zhangfeng Zhong and Liu, {Li Juan} and Dong, {Zhi Qiang} and Lihua Lu and Modi Wang and Leung, {Chung Hang} and MA, {Edmond Dik Lung} and Yitao Wang",

year = "2015",

month = jul,

day = "18",

doi = "10.1039/c5cc02728d",

language = "English",

volume = "51",

pages = "11178--11181",

journal = "Chemical Communications",

issn = "1359-7345",

publisher = "Royal Society of Chemistry",

number = "56",

}

Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database. / Zhong, Zhangfeng; Liu, Li Juan; Dong, Zhi Qiang; Lu, Lihua; Wang, Modi; Leung, Chung Hang; MA, Edmond Dik Lung; Wang, Yitao.

In: Chemical Communications, Vol. 51, No. 56, 18.07.2015, p. 11178-11181.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database

AU - Zhong, Zhangfeng

AU - Liu, Li Juan

AU - Dong, Zhi Qiang

AU - Lu, Lihua

AU - Wang, Modi

AU - Leung, Chung Hang

AU - MA, Edmond Dik Lung

AU - Wang, Yitao

PY - 2015/7/18

Y1 - 2015/7/18

N2 - 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.

AB - 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.

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DO - 10.1039/c5cc02728d

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AN - SCOPUS:84934784432

VL - 51

SP - 11178

EP - 11181

JO - Chemical Communications

JF - Chemical Communications

SN - 1359-7345

IS - 56

ER -

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

Abstract

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