小分子拟肽类氨肽酶N抑制剂的合成及初步活性  

Synthesis and APN inhibitory activities of low molecular weight peptidomimetic derivatives

作　　者：涂国刚[1] 李少华[2] 黄惠明[2] 李刚[2] 熊芳[3] 朱华伟[1] 徐文方[1] 

机构地区：[1]山东大学药学院,山东济南250012 [2]南昌大学医学院药学系,江西南昌330006 [3]南昌大学医学院第二附属医院,江西南昌330006

出　　处：《中国药物化学杂志》2008年第5期345-349,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家高技术研究发展计划项目(2007AA02Z314);国家自然科学基金重大专项研究计划课题(90713041);国家自然科学基金项目(30772654);教育部博士点基金项目(20060422029);山东省自然科学基金项目(Y2004C02)

摘　　要：目的设计合成小分子拟肽类衍生物并测定其抑制氨肽酶N(APN)的活性,研究它与酶的相互作用关系。方法通过模拟APN水解底物的过渡态,以D-丙氨酸为原料,经缩合反应合成小分子拟肽类衍生物;采用体外抑酶试验测定目标化合物抑制APN的活性。结果合成了12个未见文献报道的小分子拟肽类APN抑制剂,结构经红外光谱、核磁共振氢谱及质谱确证。结论目标化合物对APN有中等程度的抑制活性,可作为先导化合物开展进一步研究。Aim To design and synthesize low molecular weight peptidomimetic derivatives and test their APN inhibitory activities in order to investigate their interaction relationships. Methods Mimicking the transition state of substrates hydrolysed by APN, twelve low molecular weight peptidomimetic derivatives were synthesized from D-alanine, and their APN inhibitory activities were assayed in vitro. Results Twelve low molecular weight peptidomimetic APN inhibitors were synthesized and have not been reported in literature. The structures were confirmed by IR, tH-NMR and MS. Conclusion Twelve target compounds show middle degree APN inhibitory activities which are worthy of further investigation as lead compounds.

关 键 词：氨肽酶N 拟肽 过渡态 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]