- Mechanism of Inactivation of Neuronal Nitric Oxide Synthase by (S)-2-Amino-5-(2-(methylthio)acetimidamido)pentanoic Acid
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Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L-citrulline and the second messenger nitric oxide. Three mechanistic pathways are proposed for the inactivation of neuronal NOS (nNOS) by (S)-2-amino-5-(2-(methylthio)acetimidamido)pentanoic acid (1): sulfide oxidation, oxidative dethiolation, and oxidative demethylation. Four possible intermediates were synthesized. All compounds were assayed with nNOS, their IC50, KI, and kinact values were obtained, and their crystal structures were determined. The identification and characterization of the products formed during inactivation provide evidence for the details of the inactivation mechanism. On the basis of these studies, the most probable mechanism for the inactivation of nNOS involves oxidative demethylation with the resulting thiol coordinating to the cofactor heme iron. Although nNOS is a heme-containing enzyme, this is the first example of a NOS that catalyzes an S-demethylation reaction; the novel mechanism of inactivation described here could be applied to the design of inactivators of other heme-dependent enzymes.
- Tang, Wei,Li, Huiying,Doud, Emma H.,Chen, Yunqiu,Choing, Stephanie,Plaza, Carla,Kelleher, Neil L.,Poulos, Thomas L.,Silverman, Richard B.
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supporting information
p. 5980 - 5989
(2015/05/27)
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- Tetra-(tetraalkylammonium)octamolybdate catalysts for selective oxidation of sulfides to sulfoxides with hydrogen peroxide
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Tetra-(tetraalkylammonium)octamolybdate catalysts are successfully applied in the selective oxidation of various sulfides to sulfoxides with 30% aqueous hydrogen peroxide as oxidant under mild reaction conditions in 94-100% yield and 95-100% selectivity. The octamolybdate catalysts show high catalytic activity in a high ratio of substrate to catalyst (up to 10000:1) and are recyclable, with actively functional groups, including hydroxyl group and CC bonds, tolerated in the oxidation. The Royal Society of Chemistry 2009.
- Yang, Chuanbo,Jin, Qingping,Zhang, Hua,Liao, Jian,Zhu, Jin,Yu, Bin,Deng, Jingen
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supporting information; experimental part
p. 1401 - 1405
(2010/05/02)
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- Inhibitors of the advanced glycosylation of proteins and methods of use therefor
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The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with a carbonyl moiety of an early glycosylation product of such target proteins resulting from their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
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- Inhibitors of the advanced glycosylation of proteins and methods of use therefor
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The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylatin. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
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- Aminomethyl oxooxazolidinyl ethenylbenzene derivatives useful as antibacterial agents
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Aminomethyl oxooxazolidinyl ethenylbenzene derivatives, including the nitriles, sulfoxides, acetamides and nitro compounds, such as l-N-[3-[4-(E-1-methyl-2-cyanoethenyl)phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide, possess useful antibacterial activity.
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