The Establishment of an Anti-Trypanosoma Drug Screening System with Leucyl-tRNA Synthetase as an Inhibition Target
- VernacularTitle:以布氏锥虫亮氨酰tRNA合成酶为靶标的抗锥虫药物筛选系统的建立
- Author:
Guang-Wei GAO
;
Ying YAO
;
Da-Zhong DING
;
Long YE
;
Hu-Chen ZHOU
;
Da-Wei LI
;
- Publication Type:Journal Article
- Keywords:
Trypanosoma brucei LeuRS Drug screening
- From:
China Biotechnology
2006;0(12):-
- CountryChina
- Language:Chinese
-
Abstract:
Trypanosoma is a human parasite severely affecting poor tropical areas.However,current frontline drugs for Trypanosoma treatment have severe side-effects with decreased effectiveness.Based on the fact that aminoacyl-tRNA synthetase is a bonafide drug target for several microorganisms,including bacteria and fungi,it is plausible that it may also be effective target of Trypanosoma.The Trypanosoma brucei leucyl-tRNA synthetase(tbLeuRS)was cloned,expressed and purified to develop an in vitro enzymatic assay system.The assay conditions were further optimized for the effective screening of tbLeuRS inhibitors thus establishing an anti-Trypanosoma drug screening system targeting tbLeuRS.The results indicated that this system can be employed for the effective screening of anti-Trypanosoma drugs with satisfactory specificity.In addition,this system can also be used for compound optimization,as well as IC50 testing.Using this system a series of compounds are identified that are effective Trypanosoma inhibitors without toxicity to human cells.Therefore,targeting tbLeuRS may represent a new venue for the development of anti-Trypanosoma drugs.
