Hammarton Tansy C, Mottram Jeremy C, Doerig Christian
Wellcome Centre for Molecular Parasitology, Anderson College, University of Glasgow, 56 Dumbarton Road, Glasgow, G11 6NU, UK.
Prog Cell Cycle Res. 2003;5:91-101.
There is an urgent need to develop new drugs against eukaryotic parasitic protozoa such as Plasmodium, Trypanosoma and Leishmania, which cause the diseases malaria, trypanosomiasis and the leishmaniases respectively. The biology of these organisms has many unusual facets that might be exploited for drug design, and the recent availability of parasite genome sequence data has facilitated the search for novel drug targets. Here we review current understanding of the cell cycle in these parasites and show that important structural and functional differences exist between parasite and mammalian cell cycle control machineries and signal transduction pathways, which might be utilised for rational drug design. Potential targets include protein kinases from the cyclin-dependent kinase, cAMP-dependent kinase and mitogen activated protein kinase families.
迫切需要开发针对真核寄生原生动物的新药,如疟原虫、锥虫和利什曼原虫,它们分别导致疟疾、锥虫病和利什曼病。这些生物体的生物学特性有许多不同寻常的方面,可用于药物设计,而且最近可获得的寄生虫基因组序列数据有助于寻找新的药物靶点。在此,我们综述了目前对这些寄生虫细胞周期的认识,并表明寄生虫与哺乳动物细胞周期调控机制和信号转导途径之间存在重要的结构和功能差异,这些差异可用于合理的药物设计。潜在的靶点包括来自细胞周期蛋白依赖性激酶、cAMP依赖性激酶和丝裂原活化蛋白激酶家族的蛋白激酶。