摘要
目的 :内皮素 (endothelin ,ET)是重要的缩血管因子。与其受体 (ETA,ETB,ETC)作用具有很强的生物学效应。截取内皮素肽链的有效片段 ,或根据天然肽类提取物 ,利用D 型天然或特殊氨基酸 ,进行结构改造 ,寻找新型内皮素肽类拮抗剂。方法 :基于内皮素肽类拮抗剂线性三肽与线性六肽的综合结构因素 ,设计并利用王 (Wang)树脂固相法合成线性八肽 ,经HPLC纯化 ,BQ 4 85为对照物 ,作用于经ET 1诱导收缩的大鼠主动脉平滑肌膜 ETA 受体 ,用相关仪器观察此膜的舒张反应。结果与结论 :18个化学合成的八肽中 ,8个化合物与BQ 4 85活性相当 ,6个化合物在 10 6～ 10 8mol/L浓度范围内 ,呈正性反应。
ObjectiveEndothelins(ETs) are important vasocon st rictor factors and the endothelinrelated peptides binding to their receptors( ET~{*-~}A,ET~{*-~}B,ET~{*-~}C) show potent biological activities.The objective of the pre sent study was to explore novel endothelin(ET) peptidic antagonists through diss ecting.The building blocks of the peptides into different compositions, or replacing the peptide fr agment of natural extraction with D~{!<~}WT~{!=*2~}form amino acids. Met hods Basedon the comprehensi ve structural characterist ics of the linea r tripeptides and linear hexapeptides of endothelin peptidic antagonists, a seri es of novel octapeptides were designed and synthesized using Wang~{!d~}s resin soli d phase method. Having been purified by HPLC, these compounds interacted with rats~{!d~} aortic smooth muscle membrane ET~{*-~}A receptors induced and constricted b y ET1. BQ485 was synthesized through liquid phase and used as control compo und.The diasfolic change of this membrane was observed using the related instrum ent. Results and Conclusions Eight compounds showed similar activity with that of BQ485 (at 10~{*,*)*2~}9~{**~}?mol/L ). Six compounds ga ve positive react ion in the range of 10~{*,*)*2~}6~{**~}-10~{*,*)*2~}8~{**~}?mol/L. The peptides can be used as the substrate for cardiovascular pharmacological studies related to endothe lin.
出处
《军事医学科学院院刊》
CSCD
北大核心
2001年第3期190-194,共5页
Bulletin of the Academy of Military Medical Sciences
基金
军事医学科学院创新基金资助
关键词
内皮素肽类拮抗剂
八肽
合成
心血管药
主动脉平滑肌膜
高压液相色谱法
endothelin
ET antagonist
ET A receptor
BQ485
(rats) aortic smooth muscle membrane
chromatography,high pressure liquid
