Journal of Asian Natural Products Research ( IF 1.3 ) Pub Date : 2021-04-12 , DOI: 10.1080/10286020.2021.1910241 Ya-Jun Yang 1 , Ke Wang 1 , Ying Yang 1 , Fang-Fang Lai 2 , Xiao-Guang Chen 2 , Zhi-Yan Xiao 1
Abstract
Based on the interaction modes of the natural 20S proteasome inhibitors TMC-95A, we have previously discovered a dipeptide 1. To explore the SAR around compound 1, we designed and synthesized a series of dipeptides (8–38) with a fragment-based strategy. Among them, nine compounds showed significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome with IC50 values at the submicromolar level, which were comparable or even superior to the parent compound 1. Meanwhile, they displayed no significant inhibition against trypsin-like and caspase-like activities of 20S proteasome. The results suggested the feasibility to design dipeptides as novel and potent 20S proteasome inhibitors.
中文翻译:
二肽作为新型非共价20S蛋白酶体抑制剂的设计,合成和生物学评估
摘要
基于天然的20S蛋白酶体抑制剂TMC-95A的相互作用模式,我们先前已经发现了二肽1。为了探索化合物1周围的SAR ,我们设计和合成了一系列基于片段策略的二肽(8–38)。其中有9种化合物对人20S蛋白酶体的胰凝乳蛋白酶样活性具有显着的抑制活性,其IC 50值在亚微摩尔水平,与母体化合物1相当甚至更好。。同时,它们对20S蛋白酶体的胰蛋白酶样和半胱天冬酶样活性没有显着抑制作用。结果表明设计二肽作为新型有效的20S蛋白酶体抑制剂的可行性。