title: (13)C-labeled indolequinone-DTPA-Gd conjugate for NMR probing cytochrome:P450 reductase-mediated one-electron reduction.
abstract: We designed and synthesized a new class of (13)C-labeled NMR probe, (13)C-IQ-Gd, to monitor one-electron reductions by cytochrome:P450 (CYP450) reductase under hypoxic conditions. (13)C-IQ-Gd consisted of a Gd(3+)-diethylene triamine pentaacetic acid (DTPA) complex unit and an indolequinone ((13)C-IQ) unit bearing a (13)C-labeled methoxy group. The (13)C NMR signal of (13)C-IQ-Gd was suppressed because of the intramolecular paramagnetic effect of Gd(3+), whereas enzymatic reduction mediated by CYP450 reductase under hypoxic conditions yielded an intensed (13)C NMR signal due to enzymatic activation of the IQ unit followed by release of the DTPA-Gd unit from (13)C-IQ-Gd. This (13)C NMR spectral change allowed the monitoring of CYP450 reducatase-mediated one-electron reduction.
authors.affiliation: Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Komatsu
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tanabe
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Nishimoto
mesh_terms: D002247:Carbon Isotopes / Q000138:chemical synthesis / Q000737:chemistry; D004583:Electrons; D019786:Gadolinium DTPA / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D045563:Indolequinones / Q000138:chemical synthesis / Q000737:chemistry*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010084:Oxidation-Reduction
chemical_list: D002247:Carbon Isotopes; D045563:Indolequinones; D009251:NADPH-Ferrihemoprotein Reductase; D019786:Gadolinium DTPA