Design and Synthesis of C5 Methylatedl-Arginine Analogues as Active Site Probes for Nitric Oxide Synthase

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pp. 12563-12570 ◽  
Author(s):  
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Joshua J. Woodward ◽  
Michael B. Winter ◽  
William T. Beeson ◽  
Michael A. Marletta
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Silvia L. Delker ◽  
Huiying Li ◽  
Pavel Martásek ◽  
Linda J. Roman ◽  
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pp. 5296-5304 ◽  
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Elodie Lohou ◽  
Jana Sopkova-de Oliveira Santos ◽  
Pascale Schumann-Bard ◽  
Michel Boulouard ◽  
Silvia Stiebing ◽  
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Biochemistry ◽  
1996 ◽  
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pp. 9567-9575 ◽  
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Renee M. Chabin ◽  
Ermenegilda McCauley ◽  
Jimmy R. Calaycay ◽  
Theresa M. Kelly ◽  
Karen L. MacNaul ◽  
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pp. 575-578
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Fei Ma ◽  
Ping Guo ◽  
Lixun Jiang ◽  
Mingsheng Feng ◽  
Jingbo Shi ◽  
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2007 ◽  
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Etienne Derat ◽  
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2000 ◽  
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Huiying Li ◽  
C.S. Raman ◽  
Pavel Martásek ◽  
Vladimir Král ◽  
Bettie Sue S. Masters ◽  
...  

2002 ◽  
Vol 282 (6) ◽  
pp. H2167-H2172 ◽  
Author(s):  
Mathew Eric Hyndman ◽  
Subodh Verma ◽  
Robin J. Rosenfeld ◽  
Todd J. Anderson ◽  
Howard G. Parsons

The present study was designed to investigate the interaction between 5-methyltetrahydrofolate and tetrahydrobiopterin in modulating endothelial function. Tetrahydrobiopterin is a critical cofactor for nitric oxide synthase and maintains this enzyme as a nitric oxide- versus superoxide-producing enzyme. The structure of 5-methyltetrahydrofolate is similar to tetrahydrobiopterin and both agents have been shown to improve endothelium-dependent vasodilatation. We hypothesized that 5-methyltetrahydrofolate interacts with nitric oxide synthase in a fashion analogous, yet independent, of tetrahydrobiopterin to improve endothelial function. We demonstrate that 5-methyltetrahydrofolate binds the active site of nitric oxide synthase and mimics the orientation of tetrahydrobiopterin. Furthermore, 5-methyltetrahydrofolate attenuates superoxide production (induced by inhibition of tetrahydrobiopterin synthesis) and improves endothelial function in aortae isolated from tetrahydrobiopterin-deficient rats. We suggest that 5-methyltetrahydrofolate directly interacts with nitric oxide synthase to promote nitric oxide (vs. superoxide) production and improve endothelial function. 5-Methyltetrahydrofolate may represent an important strategy for intervention aimed at improving tetrahydrobiopterin bioavailability.


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