华东师范大学学报(自然科学版) ›› 2013, Vol. 2013 ›› Issue (2): 84-91.

• 生命科学 • 上一篇    下一篇

环（L-脯-L-苯丙）二肽——潜在的磷酸二酯酶抑制剂

吴 瑨1，2， 陆晓明1， 段雅乐1   

  1. 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
  • 收稿日期:2012-03-01 修回日期:2012-06-01 出版日期:2013-03-25 发布日期:2013-03-20

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

WU Jin 1，2， LU Xiao-ming 1， DUAN Ya-le 1   

  1. 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
  • Received:2012-03-01 Revised:2012-06-01 Online:2013-03-25 Published:2013-03-20

PDF

1927

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.

关键词: 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).

Key words: secondary metabolites of marine fungi, cAMP, Cyclo(L-Pro-L-Phe), phosphodiesterase inhibitor

中图分类号: