3202 J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 20
Letters
(4) Forstermann, U.; Closs, E. I.; Pollock, J . S.; Nakane, M.;
Schwarz, P.; Gath, I.; Kleinert, H. Nitric oxide synthase isozymes
- Characterization, purification, molecular cloning, and func-
tions. Hypertension 1994, 23, 1121-1131.
(14) Vadon, S.; Custot, J .; Boucher, J . L.; Mansuy, D. Synthesis and
effects on arginase and nitric oxide synthase of two novel
analogues of N-omega-hydroxyarginine, N omega-hydroxy in-
dospicine and p-hydroxy amidinophenylalanine. J . Chem. Soc.,
Perkin Trans. 1 1996, 645-648.
(5) Masters, B. S. S.; McMillan, K.; Sheta, E. A.; Nishimura, J . S.;
Roman, L. J .; Martasek, P. Neuronal nitric oxide synthase, a
modular enzyme formed by convergent evolution: Structure
studies of a cysteine thiolate-liganded heme protein that hy-
droxylates L-arginine to produce NO as a cellular signal. FASEB
J . 1996, 10, 552-558.
(6) Stuehr, D. J .; Kwon, N. S.; Nathan, C. F.; Griffith, O. W.;
Feldman, P. L.; Wiseman, J . Nω-Hydroxy-L-arginine is an
intermediate in the biosynthesis of nitric oxide from L-arginine.
J . Biol. Chem. 1991, 266, 6259-6263.
(7) Klatt, P.; Schmidt, K.; Uray, G.; Mayer, B. Multiple Catalytic
Functions of Brain Nitric Oxide Synthase - Biochemical Char-
acterization, Cofactor-Requirement, and the Role of NG-Hydroxy-
L-Arginine as an Intermediate. J . Biol. Chem. 1993, 268, 14781-
14787.
(8) Babu, B. R.; Griffith, O. W. Design of isoform-selective inhibitors
of nitric oxide synthase. Curr. Opinion Chem. Biol. 1998, 2, 491-
500.
(9) Stuehr, D. J .; Griffith, O. W. Mammalian nitric oxide synthases.
Adv. Enzymol. Relat. Areas Mol. Biol. 1992, 65, 287-346.
(10) (a) Moali, C.; Boucher, J . L.; Sari, M. A.; Stuehr, D. J .; Mansuy,
D. Substrate specificity of NO synthases: Detailed comparison
of L-arginine, homo-L-arginine, their N-omega-hydroxy deriva-
tives, and N-omega-hydroxy-nor-L-arginine. Biochemistry 1998,
37, 10453-10460. (b) Moali, C.; Brollo, M.; Custot, J .; Sari, M.
A.; Boucher, J . L.; Stuehr, D. J .; Mansuy, D. Recognition of
R-amino acids bearing various CdNOH functions by nitric oxide
synthase and arginase involves very different structural deter-
minants. Biochemistry 2000, 39, 8208-8218.
(11) Lee, Y.; Marletta, M. A.; Martasek, P.; Roman, L. J .; Masters,
B. S. S.; Silverman, R. B. Conformationally restricted arginine
analogues as alternative substrates and inhibitors of nitric oxide
synthases. Bioorg. Med. Chem. 1999, 7, 1097-1104.
(12) Grant, S. K.; Green, B. G.; Stiffey-Wilusz, J .; Durette, P. L.;
Shah, S. K.; Kozarich, J . W. Structural requirements for human
inducible nitric oxide synthase substrates and substrate ana-
logue inhibitors. Biochemistry 1998, 37, 4174-4180.
(13) Feldman, P. L.; Chi, S.; Sennequier, N.; Stuehr, D. J . Synthesis
of the L-arginine congener L-indospicine and evaluation of its
interaction with nitric oxide synthase. Bioorg. Med. Chem. Lett.
1996, 6, 111-114.
(15) Renodon-Corniere, A.; Boucher, J . L.; Dijols, S.; Stuehr, D. J .;
Mansuy, D. Efficient formation of nitric oxide from selective
oxidation of N-aryl N′-hydroxyguanidines by inducible nitric
oxide synthase. Biochemistry 1999, 38, 4663-4668.
(16) Schantl, J . G.; Tu¨rk, W. 1-(4-Chlorophenyl)-3-hydroxyguanidine
and O-acyl-derivatives. Sci. Pharm. 1989, 57, 375-380.
(17) (a) Murphy, M. E.; Noack, E. Nitric oxide assay using hemoglobin
method. Methods Enzymol. 1994, 233, 240-250. (b) Hevel, J .
M.; Marletta, M. A. Nitric-oxide synthase assays Methods
Enzymol. 1994, 233, 250-258. (c) NOS I was prepared as
described previously.10 (d) For preparation of NOS II see: Wu,
C.; Zhang, J .; Abu-Soud, H.; Ghosh, D. K.; Stuehr, D. J . High-
level expression of mouse inducible nitric oxide synthase in
Escherichia coli requires coexpression with calmodulin. Biochem.
Biophys. Res. Commun. 1996, 222, 439-444. (e) For preparation
of NOS III, see: Ghosh, S.; Gachhui, R.; Crooks, C.; Wu, C.;
Lisanti, M. P.; Stuehr, D. J . Interaction between caveolin-1 and
the reductase domain of endothelial nitric oxide synthase. J .
Biol. Chem. 1998, 273, 22267-22271.
(18) A synthesis of this compound was previously reported. Ishikawa,
T.; Misonou, T.; Ikeno, M.; Sato, K.; Sakamaki, T. Nω-Hydroxy
agmatine: A novel substance causing endothelium dependent
vasorelaxation. Biochem. Biophys. Res. Commun. 1995, 214,
145-151. It was found to exhibit relaxing properties towards
rat aorta rings.
(19) Crane, B. R.; Arvai, A. S.; Ghosh, S.; Getzoff, E. D.; Stuehr, D.
J .; Tainer, J . A. Structures of the N-omega-hydroxy-L-arginine
complex of inducible nitric oxide synthase oxygenase dimer with
active and inactive pterins. Biochemistry 2000, 39, 4608-4621.
(20) Raman, C. S.; Li, H. Y.; Martasek, P.; Kral, V.; Masters, B. S.
S.; Poulos, T. L. Crystal structure of constitutive endothelial
nitric oxide synthase: A paradigm for pterin function involving
a novel metal center. Cells 1998, 95, 939-950.
(21) Li, H.; Raman, C. S.; Martasek, P.; Kral, V.; Masters, B. S. S.;
Poulos, T. L. Mapping the active site polarity in structures of
endothelial nitric oxide synthase heme domain complexed with
isothioureas. J . Inorg. Biochem. 2000, 81, 133-139.
(22) Raman, C. S.; Li, H.; Martasek, P.; Kral, V.; Masters, B. S. S.;
Poulos, T. L. Structure of the catalytic heme domain of neuronal
nitric oxide synthase. Nitric Oxide Biol. Chem. 2000, 4, 202.
(23) Green, L. C.; Wagner, D. A.; Glogowski, J .; Skipper, P. L.;
Wishnok, J . S.; Tannenbaum, S. R. Analysis of nitrate, nitrite,
and [15N] nitrate in biological fluids. Anal. Biochem. 1982, 126,
131-138.
(24) Moali, C.; Boucher, J . L.; Renodon-Corniere, A.; Stuehr, D. J .;
Mansuy, D. Oxidations of Nω-hydroxyarginine analogues and
various N-hydroxyguanidines by NO Synthase II: Key role of
tetrahydrobiopterin in the reaction mechanism and substrate
selectivity. Chem. Res. Toxicol. 2001, 14, 202-210.
J M0155446