Homann Matthias, Lorger Mihaela, Engstler Markus, Zacharias Martin, Göringer H Ulrich
Institute of Microbiology and Genetics, Darmstadt University of Technology, Schnittspahnstrasse 10, D-64287 Darmstadt, Germany.
Comb Chem High Throughput Screen. 2006 Aug;9(7):491-9. doi: 10.2174/138620706777935324.
African trypanosomes are extracellular blood parasites that cause sleeping sickness in humans and Nagana in cattle. The therapeutics used to control and treat these diseases are very ineffective and thus, the development of new drugs is urgently needed. We have previously suggested to use trypanosome-specific RNA aptamers as tools for the development of novel trypanocidal compounds. Here, we report the selection of a 2'-NH(2)-modified RNA aptamer that binds to live trypanosomes with an affinity of 70 +/- 15 nM. The aptamer adopts a stable G-quartet structure and has a half-life in human serum of > 30 h. RNA binding is restricted to the flagellar attachment zone, located between the cell body and the flagellum of the parasite. We demonstrate that antigen-tagged preparations of the aptamer can bind to live trypanosomes and that they can be used to re-direct immunoglobulins to the parasite surface.
非洲锥虫是细胞外血液寄生虫,可导致人类昏睡病和牛的那加那病。用于控制和治疗这些疾病的疗法非常无效,因此,迫切需要开发新药。我们之前曾建议使用锥虫特异性RNA适配体作为开发新型杀锥虫化合物的工具。在此,我们报告了一种2'-NH(2)修饰的RNA适配体的筛选,该适配体以70±15 nM的亲和力结合活锥虫。该适配体采用稳定的G-四联体结构,在人血清中的半衰期>30小时。RNA结合仅限于寄生虫细胞体和鞭毛之间的鞭毛附着区。我们证明,适配体的抗原标记制剂可以结合活锥虫,并且可用于将免疫球蛋白重新导向寄生虫表面。