Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein-Ligand Interactions

doi:10.1021/acs.joc.1c00314

	Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein-Ligand Interactions
	Wang, Zhuo1,2,3 ; Chen, Tao 1,3; Liu, Hua2 ; Zhao, Xiao-Li 4; Hu, Wei-Bo 1; Yang, Hui1,2 ; Liu, Yahu A.5; Wen, Ke1,2
	2021-05-07
发表期刊	JOURNAL OF ORGANIC CHEMISTRY (IF:3.3[JCR-2023],3.2[5-Year])
ISSN	0022-3263
EISSN	1520-6904
卷号	86 期号:9 页码:6467-6477
DOI	10.1021/acs.joc.1c00314
摘要	Artificial tubular molecular pockets bearing polar functionalities on their inner surface are useful model systems for understanding the mechanisms of protein-ligand interactions in living systems. We herein report a pillar[S]arene-derived molecular tube, [P4-(OH)BPO], whose endo conformational isomer endo-[P4-(OH)BPO] possesses an inwardly pointing hydrogen-bond (H-bond) donor (OH) in its deep cavity and a strong H-bond acceptor (C=O) on its predominantly hydrophobic inner surface, rendering it a perfect protein binding pocket mimetic. A fragment-based drug design model was established using endo-[P4-(OH)BPO] and a library of various shape-complementary fragment ligands (1-38). On the A basis of the binding affinity data for fragment-pocket complexes G subset of endo-[P4-(OH)BPO] (G = 1-38), two rationally designed lead molecules (39 and 40) were identified as being able to enhance binding affinity significantly by forming H-bonds with both the donor and acceptor of endo-[P4-(OH)BPO]. The described work opens new avenues for developing pillar[n]arene-derived protein binding pocket-mimetic systems for studies of protein-ligand interactions and mechanisms of enzymatic reactions.
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收录类别	SCIE ; EI
语种	英语
WOS研究方向	Chemistry
WOS类目	Chemistry, Organic
WOS记录号	WOS:000649101400038
出版者	AMER CHEMICAL SOC
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126942
专题	物质科学与技术学院_博士生物质科学与技术学院_特聘教授组_杨辉组物质科学与技术学院_特聘教授组_文珂组物质科学与技术学院_公共科研平台_分析测试平台
通讯作者	Hu, Wei-Bo; Yang, Hui; Liu, Yahu A.; Wen, Ke
作者单位	1.Chinese Acad Sci, Shanghai Adv Res Inst, Shanghai 201210, Peoples R China; 2.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.East China Normal Univ, Dept Chem, Shanghai Key Lab Green Chem & Chem Proc, Shanghai 200062, Peoples R China; 5.ChemBridge Res Labs, Med Chem, San Diego, CA 92127 USA
第一作者单位	物质科学与技术学院
通讯作者单位	物质科学与技术学院
推荐引用方式 GB/T 7714	Wang, Zhuo,Chen, Tao,Liu, Hua,et al. Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein-Ligand Interactions[J]. JOURNAL OF ORGANIC CHEMISTRY,2021,86(9):6467-6477.
APA	Wang, Zhuo.,Chen, Tao.,Liu, Hua.,Zhao, Xiao-Li.,Hu, Wei-Bo.,...&Wen, Ke.(2021).Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein-Ligand Interactions.JOURNAL OF ORGANIC CHEMISTRY,86(9),6467-6477.
MLA	Wang, Zhuo,et al."Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein-Ligand Interactions".JOURNAL OF ORGANIC CHEMISTRY 86.9(2021):6467-6477.