环(L-脯-L-苯丙)二肽--潜在的磷酸二酯酶抑制剂  

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

作　　者：吴瑨[1,2] 陆晓明[1] 段雅乐[1] 

机构地区：[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

出　　处：《华东师范大学学报（自然科学版）》2013年第2期84-91,共8页Journal of East China Normal University(Natural Science)

基　　金：国家自然科学基金(31000574)

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.A stable GPR41 receptor cell line was used to screen candidate agonist from the sec- ondary 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-sySy 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 in duce 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-syfy and HEK293）.

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 

分 类 号：Q78[生物学—分子生物学]