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新型PEG化GLP-1受体激动剂的合成及其降血糖活性

刘颜, 李承业, 蔡星光, 孙李丹, 黄文龙

刘颜, 李承业, 蔡星光, 孙李丹, 黄文龙. 新型PEG化GLP-1受体激动剂的合成及其降血糖活性[J]. 中国药科大学学报, 2018, 49(5): 558-567. DOI: 10.11665/j.issn.1000-5048.20180507
引用本文: 刘颜, 李承业, 蔡星光, 孙李丹, 黄文龙. 新型PEG化GLP-1受体激动剂的合成及其降血糖活性[J]. 中国药科大学学报, 2018, 49(5): 558-567. DOI: 10.11665/j.issn.1000-5048.20180507
LIU Yan, LI Chengye, CAI Xingguang, SUN Lidan, HUANG Wenlong. Synthesis and preliminary anti-diabetic activity evaluation of novel PEGylated GLP-1 receptor agonists[J]. Journal of China Pharmaceutical University, 2018, 49(5): 558-567. DOI: 10.11665/j.issn.1000-5048.20180507
Citation: LIU Yan, LI Chengye, CAI Xingguang, SUN Lidan, HUANG Wenlong. Synthesis and preliminary anti-diabetic activity evaluation of novel PEGylated GLP-1 receptor agonists[J]. Journal of China Pharmaceutical University, 2018, 49(5): 558-567. DOI: 10.11665/j.issn.1000-5048.20180507

新型PEG化GLP-1受体激动剂的合成及其降血糖活性

基金项目: 国家自然科学基金资助项目(No.81673299,No.81703346)

Synthesis and preliminary anti-diabetic activity evaluation of novel PEGylated GLP-1 receptor agonists

  • 摘要: 为了得到持续稳定控制血糖的胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)类似物,将平均相对分子质量为350、550和750的单甲氧基聚乙二醇(mPEG)分别缀合到GLP-1肽链上,设计并合成了12个衍生物。初步药理活性表明,所得化合物均保留GLP-1受体激动活性,其中化合物 I - 12 降糖活性维持时间与艾塞那肽(Ex-4)和利拉鲁肽(Liraglutide)相当,具备成为新型长效化GLP-1受体激动剂的潜力。
    Abstract: In order to obtain glucagon-like peptide-1(GLP-1)analogs which can sustainedly control the levels of glucose, 12 derivatives were designed and synthesized by coupling monomethoxy polyethylene glycol(mPEG, with average molecular weights of 350, 550 and 750)to GLP-1 analogs. Preliminary pharmacological activities showed that all compounds retained GLP-1 receptor agonist activities, and the hypoglycemic activity of compound I - 12 was similar to those of Ex-4 and Liraglutide, suggesting I - 12 could be a potential long-acting GLP-1 receptor agonist.
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  • 刊出日期:  2018-10-24

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