a target-based high throughput screen yields trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity靶向性高吞吐量屏幕收益率锥虫属brucei己糖激酶小分子抑制剂抗寄生物的活动.pdfVIP
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a target-based high throughput screen yields trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity靶向性高吞吐量屏幕收益率锥虫属brucei己糖激酶小分子抑制剂抗寄生物的活动
A Target-Based High Throughput Screen Yields
Trypanosoma brucei Hexokinase Small Molecule
Inhibitors with Antiparasitic Activity
1,2 3 3 4 3
Elizabeth R. Sharlow , Todd A. Lyda , Heidi C. Dodson , Gabriela Mustata , Meredith T. Morris ,
1,2 5 6 1,2 1,2
Stephanie S. Leimgruber , Kuo-Hsiung Lee , Yoshiki Kashiwada , David Close , John S. Lazo ,
James C. Morris3*
1 University of Pittsburgh Drug Discovery Institute and Pittsburgh Molecular Libraries Screening Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of
America, 2 Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 3 Department of Genetics
and Biochemistry, Clemson University, Clemson, South Carolina, United States of America, 4 Department of Computational Biology, University of Pittsburgh, Pittsburgh,
Pennsylvania, United States of America, 5 Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North
Carolina, United States of America, 6 Graduate School of Pharmaceutical Sciences, University of Tokushima, Tokushima, Japan
Abstract
Background: The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection
of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK), an enzyme essential to
the parasite that transfers the c-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel
small molecule inhibitors of bacterially expressed Tb
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