Cyanobacterial peptides as a prototype for the design of cathepsin D inhibitors
文献类型：期刊论文
| 作者 | Xu, Hao3; Bao, Keting2; Tang, Shuai1; Ai, Jing1 ; Hu, Haiyan3; Zhang, Wei2
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| 刊名 | JOURNAL OF PEPTIDE SCIENCE
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| 出版日期 | 2017-09 |
| 卷号 | 23期号:9页码:701-706 |
| 关键词 | cathepsin D inhibitor peptides structural modification transition-state mimics |
| ISSN号 | 1075-2617 |
| DOI | 10.1002/psc.3014 |
| 文献子类 | Article |
| 英文摘要 | Cathepsin D (Cath D) is overexpressed and secreted in a number of solid tumors and involved in the progress of tumor invasion, proliferation, metastasis, and apoptosis. Inhibition of Cath D is regarded as an attractive pathway for the development of novel anticancer drugs. Our previous studies revealed that tasiamide B, a cyanobacterial peptide that contained a statine-like unit, exhibited good inhibition against Cath D and other aspartic proteases. Using this natural product as prototype, we designed and synthesized three new analogs, which bear isophthalic acid fragment at the N-terminus and isobutyl amine (1), cyclopropyl amine (2), or 3-methoxybenzyl amine (3) moiety at the C-terminus. Enzymatic assays revealed that all these three compounds showed moderate-to-good inhibition against Cath D, with IC(50)s of 15, 884, and 353nM, respectively. Notably, compound 1 showed extreme selectivity for Cath D with 576-fold over Cath E and 554-fold over BACE1, which could be a valuable template for the design of highly potent and selective Cath D inhibitors. Additionally, compound 1 showed moderated activity against HeLa cell lines with IC50 of 41.8M. Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd. |
| WOS关键词 | BETA-SECRETASE INHIBITORS ; BREAST-CANCER ; STEREOCHEMICAL REASSIGNMENT ; BIOLOGICAL EVALUATION ; ASPARTIC PROTEASE ; TASIAMIDE B ; POTENT ; DERIVATIVES ; METASTASIS ; IDENTIFICATION |
| 资助项目 | National Natural Science Foundation of China[81573340] ; 'ZhuoXue' Talent Plan of Fudan University[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000407652400004 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272515]  |
| 专题 | 药理学第一研究室 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 | Ai, Jing; Hu, Haiyan; Zhang, Wei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai, Peoples R China; 2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 3.Zhejiang Ocean Univ, Marine Sci & Technol Coll, Zhoushan 316022, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xu, Hao,Bao, Keting,Tang, Shuai,et al. Cyanobacterial peptides as a prototype for the design of cathepsin D inhibitors[J]. JOURNAL OF PEPTIDE SCIENCE,2017,23(9):701-706. |
| APA | Xu, Hao,Bao, Keting,Tang, Shuai,Ai, Jing,Hu, Haiyan,&Zhang, Wei.(2017).Cyanobacterial peptides as a prototype for the design of cathepsin D inhibitors.JOURNAL OF PEPTIDE SCIENCE,23(9),701-706. |
| MLA | Xu, Hao,et al."Cyanobacterial peptides as a prototype for the design of cathepsin D inhibitors".JOURNAL OF PEPTIDE SCIENCE 23.9(2017):701-706. |
入库方式： OAI收割
来源：上海药物研究所
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