Novel fatty chain-modified glucagon-like peptide-1 conjugates with enhanced stability and prolonged in vivo activity
文献类型：期刊论文
| 作者 | Han, Jing1; Huang, Xun2 ; Sun, Lidan1; Li, Zheng1; Qian, Hai1; Huang, Wenlong1
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| 刊名 | BIOCHEMICAL PHARMACOLOGY
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| 出版日期 | 2013-07-15 |
| 卷号 | 86期号:2页码:297-308 |
| 关键词 | Glucagon-like peptide-1 Cysteine modified Fatty chain Protracted antidiabetic effects |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2013.05.012 |
| 文献子类 | Article |
| 英文摘要 | A series of fatty chain conjugates of glucagon-like peptide-1(GLP-1) were designed and synthesized. First, eleven cysteine modified peptides (1-11) were prepared using Gly(8)-GLP-1(7-36)-NH2 peptide as a starting point. Peptides 1, 6, 9, and 11 which showed comparable GLP-1 receptor activate potency and glucose-lowering effect in vivo with Gly8-GLP-1(7-36)-NH2 were selected for second step modifications to yield conjugates 12-23. All conjugates retained significant GLP-1 receptor activate potency and more importantly exerted enhanced albumin-binding properties and in vitro plasma stability. The protracted antidiabetic effects of the most stable compound 14 were further confirmed by both multiple intraperitoneal glucose tolerance test and hypoglycemic efficacies test in vivo. Furthermore, once daily injection of compound 14 to db/db mice achieved long-term beneficial effects on HbA1c lowering and glucose tolerance. Our results suggest that compound 14 is a promising type 2 antidiabetic agent deserving further investigation. (C) 2013 Elsevier Inc. All rights reserved. |
| WOS关键词 | EXENATIDE SYNTHETIC EXENDIN-4 ; SOLID-PHASE SYNTHESIS ; RECEPTOR AGONIST ; GLYCEMIC CONTROL ; GLP-1 RECEPTOR ; DB/DB MICE ; LIRAGLUTIDE ; DERIVATIVES ; ANALOGS ; BIOACTIVITY |
| 资助项目 | National Natural Science Foundation of China[81172932] ; National Natural Science Foundation of China[81273376] ; Natural Science Foundation of Jiangsu Province[BK2012356] ; Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University[JKGZ201103] ; Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University[SKLNMZZ201212] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000321092500011 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277540]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Qian, Hai |
| 作者单位 | 1.China Pharmaceut Univ, State Key Lab Nat Med, Ctr Drug Discovery, Nanjing 210009, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 200090, Peoples R China |
| 推荐引用方式 GB/T 7714 | Han, Jing,Huang, Xun,Sun, Lidan,et al. Novel fatty chain-modified glucagon-like peptide-1 conjugates with enhanced stability and prolonged in vivo activity[J]. BIOCHEMICAL PHARMACOLOGY,2013,86(2):297-308. |
| APA | Han, Jing,Huang, Xun,Sun, Lidan,Li, Zheng,Qian, Hai,&Huang, Wenlong.(2013).Novel fatty chain-modified glucagon-like peptide-1 conjugates with enhanced stability and prolonged in vivo activity.BIOCHEMICAL PHARMACOLOGY,86(2),297-308. |
| MLA | Han, Jing,et al."Novel fatty chain-modified glucagon-like peptide-1 conjugates with enhanced stability and prolonged in vivo activity".BIOCHEMICAL PHARMACOLOGY 86.2(2013):297-308. |
入库方式： OAI收割
来源：上海药物研究所
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