| 三肽四氮唑类20S蛋白酶体抑制剂的设计、合成与活性研究 |
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| 引用本文： | Ma YH,Xu B,Cui JR,Yang ZJ,Zhang LR,Zhang LH. 三肽四氮唑类20S蛋白酶体抑制剂的设计、合成与活性研究[J]. 药学学报, 2012, 47(4): 472-478 |
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| 作者姓名： | Ma YH Xu B Cui JR Yang ZJ Zhang LR Zhang LH |
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| 作者单位： | 北京大学药学院天然药物及仿生药物国家重点实验室 |
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| 基金项目： | 国家自然科学基金资助项目(20672010) |
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| 摘 要： | 泛素-蛋白酶体途径是细胞内降解蛋白质的一种主要方式,由20S蛋白酶体来完成蛋白质的降解。本文在已经报道的肽类抑制剂的基础上,设计合成了一类三肽四氮唑化合物,通过1H NMR、MS以及元素分析对化合物结构进行了表征。活性评价结果表明,有3个目标化合物(6b、6d和6h)具有较好的抑制20S蛋白酶体类胰凝乳蛋白酶的活性。分子对接研究显示,这类新型C端基肽类化合物能通过与活性位点非共价相互作用而与蛋白酶体结合。
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| 关 键 词： | 20S蛋白酶体 抑制剂 四氮唑 三肽 药物设计 |
Design, synthesis and biological assay of novel tripeptidic tetrazoles as inhibitors of 20S proteasome |
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| Ma Yu-Heng,Xu Bo,Cui Jing-Rong,Yang Zhen-Jun,Zhang Liang-Ren,Zhang Li-He. Design, synthesis and biological assay of novel tripeptidic tetrazoles as inhibitors of 20S proteasome[J]. Acta pharmaceutica Sinica, 2012, 47(4): 472-478 |
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| Authors: | Ma Yu-Heng Xu Bo Cui Jing-Rong Yang Zhen-Jun Zhang Liang-Ren Zhang Li-He |
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| Affiliation: | State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100091, China. |
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| Abstract: | Ubiquitin-proteasome pathway (UPP) is one of the ways utilized for selective degradation of many proteins in cells, and the 20S proteasome takes the functional machinery where hydrolysis of targeted proteins takes place. Based on existing peptide inhibitors, a series of novel tripeptidic tetrazoles have been designed, synthesized, and the structures have been confirmed with 1H NMR, MS and elemental analysis. Among them, three compounds (6b, 6d and 6h) showed inhibitory activities of ChT-L of 20S proteasome. |
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