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

被引:180
作者
Verlinde, CLM
Hannaert, V
Blonski, C
Willson, M
Périé, JJ
Fothergill-Gilmore, LA
Opperdoes, FR
Gelb, MH
Hol, WGJ
Michels, PAM
机构
[1] Univ Washington, Biomol Struct Ctr, Dept Biol Struct, Seattle, WA 98195 USA
[2] Univ Catholique Louvain, Christian de Duve Inst Cellular Pathol, B-1200 Brussels, Belgium
[3] Univ Catholique Louvain, Biochem Lab, B-1200 Brussels, Belgium
[4] Univ Toulouse 3, Grp Chim Organ Biol, CNRS, UMR 5068, F-31062 Toulouse, France
[5] Univ Edinburgh, Dept Biomed Sci, Edinburgh, Midlothian, Scotland
[6] Univ Washington, Dept Chem, Seattle, WA 98195 USA
[7] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[8] Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA USA
关键词
D O I
10.1054/drup.2000.0177
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 2001 Harcourt Publishers Ltd.
引用
收藏
页码:50 / 65
页数:16
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