ICCAS OpenIR
Chemically induced dimerization of human nonpancreatic secretory phospholipase A2 by bis-indole derivatives
Zhou, Lu1; Fang, Chao1; Wei, Ping1; Liu, Shiyong1,2; Liu, Ying1; Lai, Luhua1,2
2008-06-26
Source PublicationJOURNAL OF MEDICINAL CHEMISTRY
ISSN0022-2623
Volume51Issue:12Pages:3360-3366
AbstractA series of novel bis-indole compounds, 1,omega-bis(((3-acetamino-5-methoxy-2-methylindole)-2-methylene)phenoxy)alkane, have been designed and synthesized on the basis of the enzyme structure of human nonpancreatic secretory phospholipase A2 (hnps PLA2). Their inhibition activities against hnps PLA2 were improved compared to that of the monofunctional protocompound. These bivalent ligands not only inhibited Imps PLA2 but also drove the dimerization of hnps PLA2. Their dimerization ability correlated with the linker length and position. Further study on the potent compound 5 (1,5-bis(((3-acetamino-5-methoxy-2methylindole)-2-methylene)phenoxy)pentane, IC(50) = 24 nM) revealed that cooperative binding interactions between the two enzyme molecules also contributed to the stability of the ternary complex. The combination of bivalent ligands and hnps PLA2 can be used as a novel chemically induced dimerization (CID) system for designing regulatory inhibitors.
DOI10.1021/jm7010707
Indexed BySCI ; IC
Language英语
WOS IDWOS:000256922800005
PublisherAMER CHEMICAL SOC
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/64464
Collection中国科学院化学研究所
Corresponding AuthorLiu, Ying
Affiliation1.Peking Univ, Coll Chem & Mol Engn, Beijing Natl Lab Mol Sci, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100871, Peoples R China
2.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Zhou, Lu,Fang, Chao,Wei, Ping,et al. Chemically induced dimerization of human nonpancreatic secretory phospholipase A2 by bis-indole derivatives[J]. JOURNAL OF MEDICINAL CHEMISTRY,2008,51(12):3360-3366.
APA Zhou, Lu,Fang, Chao,Wei, Ping,Liu, Shiyong,Liu, Ying,&Lai, Luhua.(2008).Chemically induced dimerization of human nonpancreatic secretory phospholipase A2 by bis-indole derivatives.JOURNAL OF MEDICINAL CHEMISTRY,51(12),3360-3366.
MLA Zhou, Lu,et al."Chemically induced dimerization of human nonpancreatic secretory phospholipase A2 by bis-indole derivatives".JOURNAL OF MEDICINAL CHEMISTRY 51.12(2008):3360-3366.
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