Frankel A E, Powell B L, Vallera D A, Neville D M
Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Curr Opin Investig Drugs. 2001 Sep;2(9):1294-301.
Most cancer patients receive chemotherapy drugs that target DNA or the cell division apparatus. Many of these patients develop multidrug-resistant tumor cells, thus, novel methods to overcome drug resistance are needed. One approach is to target tumor cell protein synthesis. Peptide toxins, which catalytically inactivate protein synthesis, have been re-engineered to selectively bind and intoxicate tumor cells. Diphtheria toxin (DT), a member of the class of peptide toxins, has been subjected to structural and genetic analysis and protein engineering for several decades. In this review, we will examine the structure, function, synthesis and pharmacology of anticancer DT conjugates.
大多数癌症患者接受靶向DNA或细胞分裂装置的化疗药物。这些患者中的许多人会产生多药耐药肿瘤细胞,因此,需要新的方法来克服耐药性。一种方法是靶向肿瘤细胞蛋白质合成。催化使蛋白质合成失活的肽毒素已被重新设计,以选择性地结合并毒害肿瘤细胞。肽毒素类成员之一的白喉毒素(DT),已经历了几十年的结构和遗传分析以及蛋白质工程研究。在本综述中,我们将研究抗癌DT偶联物的结构、功能、合成和药理学。