Rational Design of a Profluorescent Substrate for S-adenosylhomocysteine Hydrolase and its Applications in Bioimaging and Inhibitor Screening

doi:10.1021/acsami.6b09190

	Rational Design of a Profluorescent Substrate for S-adenosylhomocysteine Hydrolase and its Applications in Bioimaging and Inhibitor Screening
	Zhao, Guangjiu 1; Zheng, Daoyuan 1; Li, Dongmei 4; Wang, Jiayue 1; Wang, Yanni 1,2; Li, Chunyan 1; Han, Keli 1; Jia, Yan 1,2; Li, Peng 1; Song, Wei 3
刊名	ACS APPLIED MATERIALS & INTERFACES
	2016-10-05
卷号	8 期号:39 页码:25818-25824
关键词	S-adenosylhomocysteine Hydrolase Fluorogenic Substrate Kinetic Study Bioimaging Inhibitor Screening
ISSN号	1944-8244
DOI	10.1021/acsami.6b09190
文献子类	Article
英文摘要	S-Adenosylhomocysteine hydrolase (SAHase) is a cellular enzyme that plays a key role in the methylation process, and a potential drug target in the discovery of antiviral and anticancer agents. There is increasing interest in determining its activity in the biological and clinical fields with chemosensors but with limited success so far. Herein, we designed and developed for the first time an off/on-type of fluorogenic substrate (NADE) that is directly responsive to SAHase activity. NADE used 1,8-naphthalimide as the signal reporter and adenosine (Ade) as the reaction center; removal of the Ade moiety enhanced the fluorescence by >10-fold. Kinetic study showed that NADE followed a non-Michaelis-Menten pattern that corresponded to the allosteric behavior of SAHase. NADE showed excellent selectivity and functioned efficiently in cells, allowing the microscopic imaging of SAHase activity. NADE can also be used to identify and measure the effectiveness of inhibitors in a markedly superior way. In a word, NADE would be broadly useful in clinical applications and academic studies.
WOS关键词	ADENOSYL-L-HOMOCYSTEINE ; COLORIMETRIC ASSAY ; METHIONINE CYCLE ; ANTIVIRAL AGENTS ; ANALOGS ; DEFICIENCY ; DENSITY ; MECHANISM ; CELLS ; ADENOSYLMETHIONINE
WOS研究方向	Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000384951800020
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/169884]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Han, Keli
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, 457 Zhongshan Rd, Dalian 116023, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing, Peoples R China 3.Dalian Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China 4.Nankai Univ, Coll Pharm, Haihe Educ Pk,38 Tongyan Rd, Tianjin 300353, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Guangjiu,Zheng, Daoyuan,Li, Dongmei,et al. Rational Design of a Profluorescent Substrate for S-adenosylhomocysteine Hydrolase and its Applications in Bioimaging and Inhibitor Screening[J]. ACS APPLIED MATERIALS & INTERFACES,2016,8(39):25818-25824.
APA	Zhao, Guangjiu.,Zheng, Daoyuan.,Li, Dongmei.,Wang, Jiayue.,Wang, Yanni.,...&Song, Wei.(2016).Rational Design of a Profluorescent Substrate for S-adenosylhomocysteine Hydrolase and its Applications in Bioimaging and Inhibitor Screening.ACS APPLIED MATERIALS & INTERFACES,8(39),25818-25824.
MLA	Zhao, Guangjiu,et al."Rational Design of a Profluorescent Substrate for S-adenosylhomocysteine Hydrolase and its Applications in Bioimaging and Inhibitor Screening".ACS APPLIED MATERIALS & INTERFACES 8.39(2016):25818-25824.