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Design and Synthesis of Curcumin Analogues for in Vivo Fluorescence Imaging and Inhibiting Copper-Induced Cross-Linking of Amyloid Beta Species in Alzheimer's Disease

文献类型：期刊论文

作者Zhang, Xueli1,2,3; Tian, Yanli1,4; Li, Zeng5; Tian, Xiaoyu6; Sun, Hongbin2,3; Liu, Hong5; Moore, Anna1; Ran, Chongzhao1
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2013-11-06
卷号135期号:44页码:16397-16409
ISSN号0002-7863
DOI10.1021/ja405239v
文献子类Article
英文摘要In this article, we first designed and synthesized curcumin-based near-infrared (NIR) fluorescence imaging probes for detecting both soluble and insoluble amyloid beta (A beta) species and then an inhibitor that could attenuate cross-linking of A beta induced by copper. According to our previous results and the possible structural stereohindrance compatibility of the A beta peptide and the hydrophobic/hydrophilic property of the A beta 13-20 (HHQKLVFF) fragment, NIR imaging probe CRANAD-58 was designed and synthesized. As expected CRANAD-58 showed significant fluorescence property changes upon mixing with both soluble and insoluble A beta species in vitro. In vivo NIR imaging revealed that CRANAD-58 was capable of differentiating transgenic and wild-type mice as young as 4 months old, the age that lacks apparently visible A beta plaques and A beta is likely in its soluble forms. According to our limited studies on the interaction mechanism between CRANAD-58 and A beta, we also designed CRANAD-17 to attenuate the cross-linking of A beta 42 induced by copper. It is well-known that the coordination of copper with imidazoles on Histidine-13 and 14 (H13, H14) of A beta peptides could initialize covalent cross-linking of A beta. In CRANAD-17, a curcumin scaffold was used as an anchoring moiety to usher the designed compound to the vicinity of H13 and H14 of A beta, and imidazole rings were incorporated to compete with H13/H14 for copper binding. The results of SDS-PAGE gel and Western blot indicated that CRANAD-17 was capable of inhibiting A beta 42 cross-linking induced by copper. This raises a potential for CRANAD-17 to be considered for AD therapy.
WOS关键词POSITRON-EMISSION-TOMOGRAPHY ; PITTSBURGH COMPOUND-B ; A-BETA ; MOUSE MODEL ; TRANSGENIC MICE ; PEPTIDE AGGREGATION ; PROTEIN OLIGOMERS ; PRECURSOR PROTEIN ; MEMORY DEFICITS ; ALPHA-HELICES
资助项目[K25AG036760]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000326774300038
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/277381]  
专题药物化学研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Moore, Anna
作者单位1.Harvard Univ, Sch Med,Mol Imaging Lab, Massachusetts Gen Hosp,Dept Radiol,, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA;
2.China Pharmaceut Univ, Coll Pharm, Ctr Drug Discovery, Nanjing 210009, Jiangsu, Peoples R China;
3.China Pharmaceut Univ, Coll Pharm, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China;
4.Sun Yat Sen Univ, Zhongshan Sch Med, Dept Parasitol, Guangzhou 510275, Guangdong, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
6.Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA
推荐引用方式
GB/T 7714		 Zhang, Xueli,Tian, Yanli,Li, Zeng,et al. Design and Synthesis of Curcumin Analogues for in Vivo Fluorescence Imaging and Inhibiting Copper-Induced Cross-Linking of Amyloid Beta Species in Alzheimer's Disease[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2013,135(44):16397-16409.
APA Zhang, Xueli.,Tian, Yanli.,Li, Zeng.,Tian, Xiaoyu.,Sun, Hongbin.,...&Ran, Chongzhao.(2013).Design and Synthesis of Curcumin Analogues for in Vivo Fluorescence Imaging and Inhibiting Copper-Induced Cross-Linking of Amyloid Beta Species in Alzheimer's Disease.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,135(44),16397-16409.
MLA Zhang, Xueli,et al."Design and Synthesis of Curcumin Analogues for in Vivo Fluorescence Imaging and Inhibiting Copper-Induced Cross-Linking of Amyloid Beta Species in Alzheimer's Disease".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 135.44(2013):16397-16409.

入库方式： OAI收割

来源：上海药物研究所

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