小分子拟肽类氨肽酶N抑制剂的合成及初步活性

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。

Synthesis and APN inhibitory activities of low molecular weight peptidomimetic derivatives

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 ,¹H-NMR and MS. Conclusion Twelve target compounds show middle degree APN inhibitory activities which are worthy of further investigation as lead compounds.