环（L-脯-L-苯丙）二肽——潜在的磷酸二酯酶抑制剂

吴瑨; 陆晓明; 段雅乐

环（L-脯-L-苯丙）二肽——潜在的磷酸二酯酶抑制剂

1.
华东师范大学脑功能基因组学教育部重点实验室、上海市脑功能基因组学重点实验室,上海 200062,
2.
华东师范大学图书馆,上海 200241

详细信息

中图分类号: Q78
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出版历程
- 收稿日期: 2012-03-01
- 修回日期: 2012-06-01
- 刊出日期: 2013-03-25

Cyclo (L-Pro-L-Phe) dipeptide: the potential phosphodiesterase inhibitors

1.
Key Laboratory of Brain Functional Genomics, Ministry of Education， Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China;
2.
East China Normal University Library， Shanghai 200241， China

摘要

摘要: 利用海藻来源的黄曲霉中提取到的次级代谢产物筛选GPR41的激动剂，发现环二肽类化合物环（L-脯-L-苯丙）二肽（17号）可在多种（G41-CHO，G12-CHO，Mock-CHO，SH-sy5y和HEK293）细胞中引起细胞内cAMP水平升高.实验结果表明，17号化合物引起cAMP升高不依赖于GPCR的激活，且腺苷酸环化酶激活剂forskolin与17号化合物共处理组比fsk单独处理组cAMP进一步增加.实验结果提示，17号化合物可能是通过抑制cAMP水解，从而引起cAMP水平的持续升高.17号化合物与已知的PDE抑制剂具有相似的结构特征，可能是潜在的磷酸二酯酶抑制剂.这是首次发现环(L-脯-L-苯丙)二肽具有在多种细胞内提高cAMP浓度的作用.
- 海洋真菌次级代谢产物 /
- cAMP /
- 环（L-脯-L-苯丙）二肽 /
- 磷酸二酯酶抑制剂
Abstract: A stable GPR41 receptor cell line was used to screen candidate agonist from the secondary metabolites extracted from gulf seaweed aflatoxin c-f-3 in Putian Fujian. The cAMP results have shown that the No.17 compound Cyclo (L-Pro-L-Phe), belonging to cyclic dipeptide, is able to increase intracellular cAMP in a variety of cells (including G41-CHO, G12-CHO, Mock-CHO, SH-sy5y and HEK293). We have demonstrated that No.17 compound induced cAMP increase in a GPCR-independent manner. Co-adminstration of adenylate cyclase activating agent forskolin and No.17 compound can lead to a further increase in cAMP level compared with those treated with forskolin alone. These results have suggested that No.17 compound may induce a sustained elevation of cAMP levels by inhibiting cAMP hydrolysis. Since No.17 compound shared similar chemical structures with some known PDE inhibitors, which may be a potential of phosphodiesterase inhibitors. This is the first report that Cyclo(L-Pro-L-Phe) could regulate cAMP formation in a variety of cells (G41-CHO, G12-CHO, Mock-CHO, SH-sy5y and HEK293).
- secondary metabolites of marine fungi /
- cAMP /
- Cyclo(L-Pro-L-Phe) /
- phosphodiesterase inhibitor

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参考文献(1)

[1]

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