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锥虫是人的血液寄生虫,对热带乃至拉丁美洲贫困地区影响极大,但目前的传统治疗药物存在副作用大、有效性不断降低的问题。根据亮氨酰tRNA合成酶在微生物中可作为药物靶点的事实,在新型抗锥虫药物筛选中,通过对锥虫的亮氨酰tRNA合成酶的克隆、表达和纯化,以及该酶活性测定的优化,建立了该酶抑制物的筛选系统。筛选结果表明,这一以锥虫亮氨酰tRNA合成酶为靶标的抗锥虫药物筛选系统可以有效筛选抗锥虫化合物,选出的化合物有一定的抗锥虫特异性,并可以用于化合物的进一步优化和测定其半抑制浓度。使用这一系统筛选到了对锥虫有较好抑制作用,但对人类细胞毒性较小的一系列新型化合物,因而锥虫亮氨酰tRNA合成酶很可能成为开发有效抗锥虫药物的新靶标。
Trypanosomes are human blood parasite, which has a great impact on the tropical and even the Latin American impoverished areas. However, the current traditional therapeutic drugs have the side effects of large and decreasing effectiveness. According to the fact that leucyl tRNA synthetase can be used as a drug target in microorganisms, in the novel anti-trypanotoxies drug screening, the leucyl tRNA synthetase was cloned, expressed and purified from trypanosomes, and the activity of the enzyme The establishment of the enzyme inhibitor screening system. Screening results showed that this trypanosomiasis drug screening system targeting Trypanosyl leucyl tRNA synthetase can effectively screen for anti-trypanosome compounds. The selected compounds have certain anti-trypanosome specificity and can be used in compounds The further optimization and determination of its half-inhibitory concentration. Using this system, we have screened a series of novel compounds that have a good inhibitory effect on trypanosomata but less cytotoxic effects on human cells. Therefore, trypanosome leucyl tRNA synthetase is likely to become a new target for the development of effective anti-trypanosome drugs.