Naguib Fardos N M, El Kouni Mahmoud H
Department of Pharmacology, and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Pharmacology, and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Mol Biochem Parasitol. 2014 Mar-Apr;194(1-2):53-5. doi: 10.1016/j.molbiopara.2014.04.007. Epub 2014 Apr 28.
Competition studies and column chromatography demonstrated that adults Schistosoma mansoni contains three nucleoside kinases that can phosphorylate pyrimidine nucleosides; a non-specific deoxyriboside kinase (EC 2.7.1.145), a specific uridine kinase and a specific cytidine kinase. The non-specific deoxyriboside kinase can phosphorylate all naturally occurring pyrimidine and purine 2'-deoxyribosides. Uridine and cytidine kinases are specific for uridine and cytidine, respectively. Various nucleoside 5'-triphosphate act as phosphate donors for the three kinases albeit to different degrees. Nucleoside kinases are critical in the activation of potential anti-parasitic drugs which may be identified among the numerous available pyrimidine nucleoside analogues. The finding that S. mansoni have nucleoside kinases that differ from their host enzymes raises the possibilities that certain pyrimidine nucleoside analogues could be selectively toxic to schistosomes.
竞争研究和柱色谱法表明,曼氏血吸虫成虫含有三种可磷酸化嘧啶核苷的核苷激酶;一种非特异性脱氧核糖核苷激酶(EC 2.7.1.145)、一种特异性尿苷激酶和一种特异性胞苷激酶。非特异性脱氧核糖核苷激酶可磷酸化所有天然存在的嘧啶和嘌呤2'-脱氧核糖核苷。尿苷激酶和胞苷激酶分别对尿苷和胞苷具有特异性。各种核苷5'-三磷酸作为三种激酶的磷酸供体,尽管程度不同。核苷激酶在潜在抗寄生虫药物的激活中起关键作用,这些药物可能在众多可用的嘧啶核苷类似物中被发现。曼氏血吸虫具有与其宿主酶不同的核苷激酶这一发现增加了某些嘧啶核苷类似物可能对血吸虫具有选择性毒性的可能性。