摘要
核糖核酸酶(RNases)是一个超家族酶,自20世纪60年代以来被广泛研究。长期以来,这类分泌酶作为蛋白质化学的重要模型被研究,如折叠、稳定性和酶催化。自从发现RNases对多种恶性细胞显示出细胞毒活性以来,近年来的研究主要集中在工程RNases的生物学功能和医学应用上。在这篇综述中,我们描述了RNases抗肿瘤活性的结构、功能和机制。它们在转录和翻译的十字路口运作,优先降解tRNA。结果,这抑制了蛋白质的合成,诱导细胞凋亡,并导致癌细胞的死亡。当RNases与单克隆抗体结合时,这种效应可以增强数千倍。这种被称为免疫酶(immunoRNases)的组合,已经在体外和动物模型中证明了对癌细胞的选择性抗肿瘤活性。本文综述了工程化核糖核酸酶和免疫化核糖核酸酶作为治疗不同类型癌症的新药物的现状。此外,我们描述我们的实验结果来自已发表或以前未发表的研究,并与其他科学信息进行比较。
关键词: 细胞凋亡,肿瘤治疗,临床试验,细胞毒性,免疫酶,核糖核酸酶。
图形摘要
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