Eastman Richard T, Buckner Frederick S, Yokoyama Kohei, Gelb Michael H, Van Voorhis Wesley C
Department of Pathobiology, University of Washington, Seattle, WA, USA.
J Lipid Res. 2006 Feb;47(2):233-40. doi: 10.1194/jlr.R500016-JLR200. Epub 2005 Dec 7.
Protein farnesylation is a form of posttranslational modification that occurs in most, if not all, eukaryotic cells. Inhibitors of protein farnesyltransferase (PFTIs) have been developed as anticancer chemotherapeutic agents. Using the knowledge gained from the development of PFTIs for the treatment of cancer, researchers are currently investigating the use of PFTIs for the treatment of eukaryotic pathogens. This "piggy-back" approach not only accelerates the development of a chemotherapeutic agent for protozoan pathogens but is also a means of mitigating the costs associated with de novo drug design. PFTIs have already been shown to be efficacious in the treatment of eukaryotic pathogens in animal models, including both Trypanosoma brucei, the causative agent of African sleeping sickness, and Plasmodium falciparum, one of the causative agents of malaria. Here, current evidence and progress are summarized that support the targeting of protein farnesyltransferase for the treatment of parasitic diseases.
蛋白质法尼基化是一种翻译后修饰形式，几乎在所有真核细胞中都会发生。蛋白质法尼基转移酶抑制剂（PFTIs）已被开发用作抗癌化疗药物。利用从开发用于治疗癌症的PFTIs中获得的知识，研究人员目前正在研究将PFTIs用于治疗真核病原体。这种“搭便车”方法不仅加速了用于原生动物病原体的化疗药物的开发，也是降低与从头药物设计相关成本的一种手段。PFTIs已被证明在动物模型中对真核病原体的治疗有效，这些病原体包括非洲昏睡病的病原体布氏锥虫以及疟疾的病原体之一恶性疟原虫。在此，总结了支持将蛋白质法尼基转移酶作为治疗寄生虫病靶点的当前证据和进展。
