Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity
文献类型：期刊论文
| 作者 | Sun, Lidan4; Huang, Xun5 ; Han, Jing1,4; Cai, Xingguang4; Dai, Yuxuan4; Chu, Yingying4; Wang, Chuandong2,3; Huang, Wenlong4; Qian, Hai4
|
| 刊名 | BIOCHEMICAL PHARMACOLOGY
 |
| 出版日期 | 2016-06-15 |
| 卷号 | 110页码:80-91 |
| 关键词 | Ex-4 Cysteine modified Fatty chain Protracted antidiabetic effects |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2016.04.016 |
| 文献子类 | Article |
| 英文摘要 | The therapeutic utility of exenatide (Ex-4) is limited due to short plasma half-life of 2.4 h and thus numerous approaches have been used to obtain a longer action time. However, such strategies often attend to one thing and lose another. The study aimed to identify a candidate with balanced glucoregulatory activity and prolonged in vivo activity. A series of fatty chain conjugates of Ex-4 were designed and synthesized. First, thirteen cysteine modified peptides (1-13) were prepared. Peptides 1, 10, and 13 showed improved glucagon-like peptide-1 (GLP-1) receptor activate potency and were thus selected for second step modifications to yield conjugates I-1-I-9. 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 I-3 were further confirmed by both multiple intraperitoneal glucose tolerance test and hypoglycemic efficacies test in vivo. Furthermore, once daily injection of I-3 to streptozotocin (STZ) induced diabetic mice achieved long-term beneficial effects on hemoglobin A1C (HbA1C) lowering and glucose tolerance. Once daily injection of I-3 to diet induced obesity (DIO) mice also achieved favorable effects on food intake, body weight, and blood chemistry. Our results suggested that I-3 was a promising agent deserving further investigation to treat obesity patients with diabetes. (C) 2016 Elsevier Inc. All rights reserved. |
| WOS关键词 | GLUCAGON-LIKE PEPTIDE-1 ; ACID-CONJUGATED EXENDIN-4 ; SOLID-PHASE SYNTHESIS ; BETA-CELL ; BIOLOGICAL-ACTIVITY ; PLASMA STABILITY ; ZUCKER RATS ; RECEPTOR ; DERIVATIVES ; MICE |
| 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:000377738400008 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275997]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Huang, Wenlong; Qian, Hai |
| 作者单位 | 1.Jiangsu Normal Univ, Sch Chem & Chem Engn, Xuzhou 221116, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Med, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200030, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China 4.China Pharmaceut Univ, Ctr Drug Discovery, Jiangsu Key Lab Drug Discovery Metab Dis, State Key Lab Nat Med, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 200090, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Sun, Lidan,Huang, Xun,Han, Jing,et al. Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity[J]. BIOCHEMICAL PHARMACOLOGY,2016,110:80-91. |
| APA | Sun, Lidan.,Huang, Xun.,Han, Jing.,Cai, Xingguang.,Dai, Yuxuan.,...&Qian, Hai.(2016).Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity.BIOCHEMICAL PHARMACOLOGY,110,80-91. |
| MLA | Sun, Lidan,et al."Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity".BIOCHEMICAL PHARMACOLOGY 110(2016):80-91. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。