Inhibition of thrombin by functionalized C-60 nanoparticles revealed via in vitro assays and in silico studies

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Inhibition of thrombin by functionalized C-60 nanoparticles revealed via in vitro assays and in silico studies
	Liu, Yanyan; Fu, Jianjie; Pan, Wenxiao; Xue, Qiao; Liu, Xian; Zhang, Aiqian
刊名	JOURNAL OF ENVIRONMENTAL SCIENCES-CHINA
	2018
卷号	63 页码:285-295
关键词	Thrombin C-60 nanoparticle (NP) Surface modification Activity inhibition Quantitative nanostructure-activity relationship Molecular docking
ISSN号	1001-0742
文献子类	Article
英文摘要	The studies on the human toxicity of nanoparticles (NPs) are far behind the rapid development of engineered functionalized NPs. Fullerene has been widely used as drug carrier skeleton due to its reported low risk. However, different from other kinds of NPs, fullerene-based NPs (C-60 NPs) have been found to have an anticoagulation effect, although the potential target is still unknown. In the study, both experimental and computationalmethods were adopted to gain mechanistic insight into the modulation of thrombin activity by nine kinds of C-60 NPs with diverse surface chemistry properties. In vitro enzyme activity assays showed that all tested surface-modified C-60 NPs exhibited thrombin inhibition ability. Kinetic studies coupled with competitive testing using 3 known inhibitors indicated that six of the C-60 NPs, of greater hydrophobicity and hydrogen bond (HB) donor acidity or acceptor basicity, acted as competitive inhibitors of thrombin by directly interacting with the active site of thrombin. A simple quantitative nanostructure-activity relationshipmodel relating the surface substituent properties to the inhibition potential was then established for the six competitive inhibitors. Molecular docking analysis revealed that the intermolecular HB interactions were important for the specific binding of C-60 NPs to the active site canyon, while the additional stability provided by the surface groups through van der Waals interaction also play a key role in the thrombin binding affinity of the NPs. Our results suggest that thrombin is a possible target of the surface-functionalized C-60 NPs relevant to their anticoagulation effect. (C) 2017 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/40969]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Liu, Yanyan,Fu, Jianjie,Pan, Wenxiao,et al. Inhibition of thrombin by functionalized C-60 nanoparticles revealed via in vitro assays and in silico studies[J]. JOURNAL OF ENVIRONMENTAL SCIENCES-CHINA,2018,63:285-295.
APA	Liu, Yanyan,Fu, Jianjie,Pan, Wenxiao,Xue, Qiao,Liu, Xian,&Zhang, Aiqian.(2018).Inhibition of thrombin by functionalized C-60 nanoparticles revealed via in vitro assays and in silico studies.JOURNAL OF ENVIRONMENTAL SCIENCES-CHINA,63,285-295.
MLA	Liu, Yanyan,et al."Inhibition of thrombin by functionalized C-60 nanoparticles revealed via in vitro assays and in silico studies".JOURNAL OF ENVIRONMENTAL SCIENCES-CHINA 63(2018):285-295.