title: An NMR Biochemical Assay for Fragment-Based Drug Discovery: Evaluation of an Inhibitor Activity on Spermidine Synthase of Trypanosoma cruzi.
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.
authors.affiliation: Biomedical Research Institute , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, 305-8566, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamasaki
authors.affiliation: Biomedical Research Institute , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, 305-8566, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Tani
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc. , 21 Miyukigaoka, Tsukuba, 305-8585, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tateishi
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc. , 21 Miyukigaoka, Tsukuba, 305-8585, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Tanabe
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc. , 21 Miyukigaoka, Tsukuba, 305-8585, Japan.
authors.forename: Ichiji
authors.initials: I
authors.lastname: Namatame
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc. , 21 Miyukigaoka, Tsukuba, 305-8585, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Niimi
authors.affiliation: Biomedical Research Institute , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, 305-8566, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Biomedical Research Institute , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, 305-8566, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakashita
mesh_terms: D014355:Chagas Disease / Q000188:drug therapy; D003514:Cyclohexylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004789:Enzyme Activation / Q000187:drug effects; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D003514:Cyclohexylamines; C059116:4-methylcyclohexylamine; D011436:Spermidine Synthase