硝基精氨酸赖氨酸三肽合成及其对一氧化氮合酶的抑制作用  

Synthesis of N^G-nitro-Arginine-Lysine Tripeptide and Its Inhibition on NOS

作　　者：杨军珂[1] 吴赛珠[1] 周可祥[1] 彭师奇[2] 孟素荣[1] 吴宗贵[3] 阮云军[1] 董凤英[1] 

机构地区：[1]第一军医大学南方医院心内科,广东广州510515 [2]北京医科大学药学院中德联合实验室,北京100853 [3]第二军医大学长征医院心内科,上海200003

出　　处：《中国药物化学杂志》2001年第1期13-16,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家新药研究与开发基金"抗败血性休克的NOS拮抗剂设计与筛选"项目的资助!(96 90 1 0 5 44 )

摘　　要：液相合成法合成了由左旋精氨酸、左旋赖氨酸组成的硝基精氨酸 赖氨酸三肽HCl·Arg(NO2 ) Lys(OCH3) Arg(NO2 )·HCl,并研究其对原生型一氧化氮合酶 (cNOS)和诱生型一氧化氮合酶 (iNOS)的抑制程度。培养大鼠腹腔巨噬细胞实验结果显示 :目标化合物 (10 -4 mol/L)可显著抑制巨噬细胞产生一氧化氮 (NO) (P <0 0 1) ,较NG 硝基 左旋精氨酸 (L NNA)作用增强 (P <0 0 1) ;且可显著减少巨噬细胞内环磷酸鸟苷 (cGMP)水平 (P <0 0 1) ,较L NNA作用增强 (P <0 0 5 )。大鼠离体主动脉抑制实验结果显示 :与L NNA相比 ,目标化合物 (1 5× 10 -4 mol/L)对cNOS的抑制程度减小 (P <0 0 5 )。活性实验结果表明 :目标化合物抑制大鼠腹腔巨噬细胞内iN OS活性显著强于L NNA ,而抑制大鼠血管壁cNOS活性却弱于L NNA。A new tripeptide HCl·Arg(NO 2) Lys(OCH 3) Arg(NO 2)·HCl containing L Arginine and L Lysine was synthesized by the solusion phase synthesis,the inhibition of the target compound on cNOS and iNOS were studied too.Results of rat peritoneal macrophage culture were:The target compound(10 -4 mol/L)could significantly inhibit macrophages to produce NO( P <0 01),and had more potency than L NNA( P <0 01);it could also significantly reduce the level of cGMP in macrophages( P <0 01),and had more potency than L NNA( P <0 05).Results of rat isolated aortic ring incubation was:The target compound(1 5×10 -4 mol/L)played less inhibitory role in cNOS of rat aorta,compared with L NNA( P <0 05).It is clear by the activity experiment,that the target compound inhibits iNOS in rat peritoneal macrophages more potently than L NNA and inhibits cNOS less potently than L NNA.

关 键 词：一氧化氮 一氧化氮合酶 一氧化氮合酶抑制剂 硝基精氨酸-赖氨酸三肽 

分 类 号：R914[医药卫生—药物化学]