5位、6位、8位氨基酸残基对 LHRH 类似物生物活性的影响  

EFFECTS OF AMINO ACID RESIDUES AT POSITION 5,6,8 ON ACTIVITY OF LHRH ANALOGUE

作　　者：周美华[1] 周杰 韩桂珍[1] 张雅文[2] 褚云鸿[1] 

机构地区：[1]上海医科大学药理教研室,上海200032 [2]苏州大学化学系,苏州215000

出　　处：《中国医药工业杂志》1991年第5期208-210,共3页Chinese Journal of Pharmaceuticals

基　　金：本课题得到高等学校博士学科点专项科研基金资助

摘　　要：采用假孕大鼠黄体细胞体外培养和孕酮放射免疫(RIA)测定法,比较通式为 pGlu^1-His^2-Trp-Ser^4-A^5-B^6-C^7-D^8-Pro^9-Gly^10-NH_2的七种不同结构的 LHRH 类似物抑制黄体细胞分泌孕酮作用的强弱,初步分析其构效关系。结果表明:(1)5位以 His 取代优于5位不取代者;(2)8位 Gln 取代优于 Leu 取代;(3)6位 D 型氨基酸取代提高活性的顺序是 D-Trp^6>D-Leu^6>D-Ala^6、D_2Nal^6。本文结果提示大鼠黄体细胞培养法可取代垂体细胞培养法作为 LHRH 类似物生物活性的初步定量。The pseudopregnant rat luteal cell culture and the progesteroneradioimmuno-assay were used to compare the inhibitory effect of seven LHRH.analogues with general formula pGlu^1-His^2-Trp^3-Ser^4-A^5-B^6-C^7-D^8-Pro^9-Gly^(10)-NH_2 onthe progesterone secretion of luteal cells.The results of LHRH-A activity comparisonshowed that:(1)the His^5 substitution was greater than the original LHRH;(2)Gln^8substitution was greater than Leu^8,(3)D-amino acid residues at position 6 enhancedthe activity as follows:D-Trp^6>D-Leu^6>D-Ala^6,D_2Nal^6.The results suggestedthat the luteal cell culture method could be used as a primary screening methodof LHRH-A instead of the more expensive pituitary cell culture technique.

关 键 词：LHRH 黄体细胞 孕酮 构效关系 

分 类 号：R965[医药卫生—药理学]