链霉菌I06A-02832产生的VEGFR2-CD拮抗剂发现研究  

Discovery on antagonists of VEGFR2-CD produced by Streptomyces strain I06A-02832

作　　者：蒋忠科[1] 张洋[1] 郭连宏[1] 姜蓉[1] 孙承航[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《中国抗生素杂志》2014年第6期408-412,421,共6页Chinese Journal of Antibiotics

基　　金：国家自然科学基金(81172963);十二五"重大新药创制"科技重大专项(2012ZX09301-002-001-018);2012年中国医学科学院医药生物技术研究所中央级公益性科研院所基本科研业务专项(IMBF201204);北京市自然科学基金资金项目(7133249);高等学校博士学科点专项科研基金新教师类项目(No.20131106120027)

摘　　要：目的分离鉴定链霉菌I06A-02832发酵液中具血管内皮细胞生长因子受体-2酪氨酸激酶(VEGFR2-CD)抑制活性的次生代谢产物。方法采用大孔吸附树脂、Se phadex LH-20、HPLC等分离手段对次生代谢产物进行分离纯化;通过质谱(MS)、核磁共振波谱(NMR)对其结构进行鉴定,以ELISA法检测其次生代谢产物对VEGFR2-CD的拮抗活性。结果分离得到两个环二肽类次生代谢产物:2832B和2832C;化合物2832B的化学结构与环(脯氨酸-酪氨酸)一致,化合物2832C的化学结构与环(苯丙氨酸-甘氨酸)一致,均对VEGFR2-CD表现出一定的抑制活性。结论化合物2832B和2832C是具有VEGFR2-CD活性的环二肽类次生代谢产物,本研究首次报道它们具有VEGFR2-CD抑制活性。Objective To discover antagonists of VEGFR2-CD from the fermentation broth produced by streptomyces strain I06A-02832. Methods Under the guidance of ELISA assay against VEGFR2-CD, Compounds 2832B and 2832C were isolated and purified by combination of different column chromatographies and HPLC. The structures of compounds 2832B and C were identified by combination of analysis of UV, IR, MS and 1D-NMR, 2D-NMR. Results Compounds 2832B and 2832C were purified and structurally identified as cyclic dipeptides, and were the same with cyclo-（Pro-Tyr） and cyclo-（Phe-Gly） respectively. Compounds 2832B and 2832C showed weak antagonistic activity against VEGFR2-CD by ELISA assay. Conclusion They are firstly reported compounds 2832B and 2832C had antagonistic activity against VEGFR2-CD.

关 键 词：VEGFR2-CD 链霉菌 环二肽 拮抗剂 

分 类 号：R979.5[医药卫生—药品]