| Abstract
| - 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-α-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.
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