title: Potent inhibition of macrophomate synthase by reaction intermediate analogs.
abstract: Potent inhibitors for macrophomate synthase, which has recently been found to catalyze a highly unusual five-step chemical transformation, were explored. Among 11 oxalacetate analogs tested, only three analogs had moderate to relatively strong inhibitory activities (I50 1.3-8.1 mM). On the other hand, among 35 bicyclic intermediate analogs synthesized, two diacids were found to be the most potent inhibitors (I50 0.80, 0.84 mM) which had a much higher affinity than that of the natural substrate 2-pyrone. (-)-Enantiomers of the diacids showed 30 times stronger activity (I50 0.34, 0.41 mM) than (+)-ones. The I50/Km values (0.20, 0.24) showed their potent inhibitions. Competitive inhibitions were observed in two representative inhibitors.
authors.affiliation: Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo, Japan. hoik@chem.agr.hokudai.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Oikawa
authors.forename: K
authors.initials: K
authors.lastname: Yagi
authors.forename: S
authors.initials: S
authors.lastname: Ohashi
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Mie
authors.forename: A
authors.initials: A
authors.lastname: Ichihara
authors.forename: M
authors.initials: M
authors.lastname: Honma
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010071:Oxaloacetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D010071:Oxaloacetates; D011753:Pyrones; C408144:macrophomate synthase