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Synthesis, evaluation and molecular dynamics study of human toll-like receptor 2/6 specific monoacyl lipopeptides as candidate immunostimulants

文献类型：期刊论文

作者Zhu, Yueyue5; Liu, Bo3,4; Chen, Zonglong5; Wang, Xianyang5; Wang, Yujie5; Zhang, Wenhong1,2; Wang, Sen1,2; Zhang, Mingming5; Li, Yingxia5
刊名BIOORGANIC CHEMISTRY
出版日期2023-12-01
卷号141页码:17
ISSN号0045-2068
关键词Toll -like receptor 2/6 agonists PamCS Structure-activity relationship Lipopeptide Immunostimulants
DOI10.1016/j.bioorg.2023.106823
通讯作者Wang, Sen() ; Zhang, Mingming() ; Li, Yingxia(liyx417@fudan.edu.cn)
英文摘要TLR2 agonists typified by the S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-R-cysteinyl-S-serine (Pam2CS) motif have exhibited powerful immunostimulatory activities. Based on simplified monoacyl lipopeptide (Carbamate-linked N-Ac PamCS), we describe interesting SAR investigations where modifications are done to alter the size of substituents on the cysteine amine, introduce ionizable groups to the terminal and insert aromatic substitutions to the aliphatic chain. Our structural modifications have led to a highly specific human TLR2/6 agonist 14a (EC50 = 0.424 nM), which behaves like Pam2CSK4 by inducing NF-kappa B activation to trigger downstream signaling pathways, such as subsequent phosphorylation of related proteins (p65, p38) and production of key inflammatory cytokines (IL-6, IL-1 beta, TNF-alpha). Importantly, the ability to stimulate enhanced T cell response compared to Carbamate-linked N-Ac PamCS makes compound 14a a further potential candidate immunostimulant.
WOS关键词INNATE IMMUNITY ; ACTIVATION ; AGONISTS ; VACCINE
资助项目National Natural Science Foundation of China[81973178] ; Shanghai Municipal Science and Technology Major Project[HS2021SHZX001]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:001077999900001
源URL[http://119.78.100.183/handle/2S10ELR8/307342]  
专题新药研究国家重点实验室
通讯作者Wang, Sen; Zhang, Mingming; Li, Yingxia
作者单位1.Shanghai Huashen Inst Microbes & Infect, 6 Lane 1220 Huashan Rd, Shanghai 200052, Peoples R China
2.Fudan Univ, Dept Infect Dis, Shanghai Key Lab Infect Dis & Biosafety Emergency, Natl Med Ctr Infect Dis,Huashan Hosp, Shanghai 200040, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Yueyue,Liu, Bo,Chen, Zonglong,et al. Synthesis, evaluation and molecular dynamics study of human toll-like receptor 2/6 specific monoacyl lipopeptides as candidate immunostimulants[J]. BIOORGANIC CHEMISTRY,2023,141:17.
APA Zhu, Yueyue.,Liu, Bo.,Chen, Zonglong.,Wang, Xianyang.,Wang, Yujie.,...&Li, Yingxia.(2023).Synthesis, evaluation and molecular dynamics study of human toll-like receptor 2/6 specific monoacyl lipopeptides as candidate immunostimulants.BIOORGANIC CHEMISTRY,141,17.
MLA Zhu, Yueyue,et al."Synthesis, evaluation and molecular dynamics study of human toll-like receptor 2/6 specific monoacyl lipopeptides as candidate immunostimulants".BIOORGANIC CHEMISTRY 141(2023):17.

入库方式： OAI收割

来源：上海药物研究所

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