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糖酵解作为新型抗锥虫药物设计的靶点。

Glycolysis as a target for the design of new anti-trypanosome drugs.

作者信息

Verlinde C L, Hannaert V, Blonski C, Willson M, Périé J J, Fothergill-Gilmore L A, Opperdoes F R, Gelb M H, Hol W G, Michels P A

机构信息

Department of Biological Structure, Biomolecular Structure Center, University of Washington, Seattle, USA.

出版信息

Drug Resist Updat. 2001 Feb;4(1):50-65. doi: 10.1054/drup.2000.0177.

Abstract

Glycolysis is perceived as a promising target for new drugs against parasitic trypanosomatid protozoa because this pathway plays an essential role in their ATP supply. Trypanosomatid glycolysis is unique in that it is compartmentalized, and many of its enzymes display unique structural and kinetic features. Structure- and catalytic mechanism-based approaches are applied to design compounds that inhibit the glycolytic enzymes of the parasites without affecting the corresponding proteins of the human host. For some trypanosomatid enzymes, potent and selective inhibitors have already been developed that affect only the growth of cultured trypanosomatids, and not mammalian cells.

摘要

糖酵解被认为是开发抗寄生锥虫原生动物新药的一个有前景的靶点,因为该途径在它们的ATP供应中起着至关重要的作用。锥虫的糖酵解是独特的,因为它是分隔的,并且其许多酶表现出独特的结构和动力学特征。基于结构和催化机制的方法被用于设计能够抑制寄生虫糖酵解酶而不影响人类宿主相应蛋白质的化合物。对于一些锥虫酶,已经开发出了强效且选择性的抑制剂,这些抑制剂仅影响培养的锥虫的生长,而不影响哺乳动物细胞。

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