First Non--Amino Acid Guanidines Acting as Efficient NO Precursors upon Oxidation by NO-Synthase II or Activated Mouse Macrophages
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- 作者：Sylvie Dijols ; Jean-Luc Boucher ; Michel Lepoivre ; David Lefevre-Groboillot ; Magali Moreau ; Yves Frapart ; Eleni Rekka ; Abigail L. Meade ; Dennis J. Stuehr ; and Daniel Mansuy
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：July 30, 2002
- 年：2002
- 卷：41
- 期：30
- 页码：9286 - 9292
- 全文大小：68K
- 年卷期：v.41,no.30(July 30, 2002)
- ISSN：1520-4995
文摘
A study of the oxidation of a series of guanidines related to L-arginine (L-Arg) and of variousalkyl- and arylguanidines, by recombinant NO-synthase II (NOS II), led us to the discovery of the firstnon-
-amino acid guanidine substrate of NOS, acting as an efficient NO precursor. This compound,3-(trifluoromethyl)propylguanidine, 4, led to a rate of NO formation (kcat = 220 ± 50 min-1) only 2times lower than that of L-Arg. Formation of 1 mol of NO upon NOS II-catalyzed oxidation of 4 occurredwith consumption of 2.9 mol of NADPH, which corresponds to a 52% coupling between electron transferand oxygenation of its guanidine function. Its oxidation by activated mouse macrophages in an L-Arg-free medium resulted in NO2- formation that was inhibited by classical NOS inhibitors with a rate only2-3 times lower than that observed with L-Arg itself. These results open the way toward the research ofselective, stable guanidine substrates of NOS that could be interesting, new NO donors after in situ oxidationby a given NOS isoform.
-amino acid guanidine substrate of NOS, acting as an efficient NO precursor. This compound,3-(trifluoromethyl)propylguanidine, 4, led to a rate of NO formation (kcat = 220 ± 50 min-1) only 2times lower than that of L-Arg. Formation of 1 mol of NO upon NOS II-catalyzed oxidation of 4 occurredwith consumption of 2.9 mol of NADPH, which corresponds to a 52% coupling between electron transferand oxygenation of its guanidine function. Its oxidation by activated mouse macrophages in an L-Arg-free medium resulted in NO2- formation that was inhibited by classical NOS inhibitors with a rate only2-3 times lower than that observed with L-Arg itself. These results open the way toward the research ofselective, stable guanidine substrates of NOS that could be interesting, new NO donors after in situ oxidationby a given NOS isoform.