An NMR Biochemical Assay for Fragment-Based Drug Discovery: Evaluation of an Inhibitor Activity on Spermidine Synthase of Trypanosoma cruzi

Journal of Medicinal Chemistry
Kazuhiko YamasakiHitoshi Sakashita

Abstract

Although NMR in fragment-based drug discovery is utilized almost exclusively to evaluate physical binding between molecules, it should be also a powerful tool for biochemical assay, evaluating inhibitory effect of compounds on enzymatic activity. Time-dependent spectral change in real-time monitoring or inhibitor concentration-dependent spectral change after constant-time reaction was processed by factor analysis, by which reaction rate or IC50 value was obtained. Applications to spermidine synthase of Trypanosoma cruzi, which causes Chagas disease, are described.

References

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Jun 25, 2004·Journal of Medicinal Chemistry·Daniel A ErlansonTom O'Brien
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Sep 14, 2013·Analytical Chemistry·Kazuhiko YamasakiTakamitsu Kohzuma
Sep 4, 2015·Acta Crystallographica. Section D, Biological Crystallography·Yasushi AmanoHitoshi Sakashita

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Citations

May 27, 2017·Chemical Biology & Drug Design·Juliana da Fonseca Rezende E MelloGustavo Henrique Goulart Trossini
Oct 20, 2018·The Journal of Biological Chemistry·Margaret A Phillips
Sep 13, 2019·Expert Opinion on Drug Discovery·Miaomiao Liu, Ronald J Quinn
Sep 28, 2018·Current Medicinal Chemistry·Alan TaleviMarcelo Comini
Apr 9, 2021·Journal of Biochemistry·Kazuhiko YamasakiHiroto Suematsu

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