N(ω)-nitroarginine-containing dipeptide amides. Potent and highly selective inhibitors of neuronal nitric oxide synthase

Journal of Medicinal Chemistry

Volumn 42, Issue 16, 1999, Pages 3147-3153

  Huang, Hui ^a   Martasek, Pavel ^b   Roman, Linda J ^b   Masters, Bettie Sue Siler ^b   Silverman, Richard B ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; CALMODULIN; CITRULLINE; FLAVINE ADENINE NUCLEOTIDE; FLAVINE MONONUCLEOTIDE; HEME DERIVATIVE; N(G) NITROARGININE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE INHIBITOR; PEPTIDE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; TETRAHYDROBIOPTERIN;

AMINO ACID SEQUENCE; ARTICLE; BLOOD PRESSURE MONITORING; CATALYSIS; DRUG POTENCY; ELECTRICITY; ENZYME INHIBITION; HYDROGEN BOND; IMMUNE RESPONSE; LONG TERM POTENTIATION; NEUROTRANSMISSION; OXIDATION; SEQUENCE HOMOLOGY; SYNTHESIS; THROMBOCYTE AGGREGATION;

ANIMALS; CATTLE; DIPEPTIDES; ENZYME INHIBITORS; MICE; NEURONS; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE TYPE II; NITROARGININE; RATS;

EID: 0033549862     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990111c     Document Type: Article

References (46)

1. Kerwin, J. F., Jr.; Lancaster, J. R., Jr.; Feldman, P. L. Nitric oxide: a new paradigm for second messengers. J. Med. Chem. 1995, 38, 4342-62.
2. Kerwin, J. F., Jr.; Heller, M. The arginine-nitric oxide pathway: A target for new drugs. Med. Res. Rev. 1994, 14, 23-74.
3. Stuehr, D. J.; Griffith, O. W. Mammalian nitric oxide synthases. Adv. Enzymol. Relat. Areas Mol. Biol. 1992, 65, 287-346.
4. Knowles, R. G.; Moncada, S. Nitric oxide synthases in Mammals. Biochem. J. 1994, 198, 249-258.
5. (a) Choi, D. W.; Rothman, S. M. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu. Rev. Neurosci. 1990, 13, 171-182.
6. (b) Garthwaite, J. In The NMDA Receptor; Watkins, J. C., Collingridge, G. L., Eds.; Oxford University Press: Oxford, England, 1989; pp 187-205.
7. Thomsen, L. L.; Iversen, H. K.; Lassen, L. H.; Olesen, J. The role of nitric oxide in migraine pain. CNS Drugs 1994, 2, 417-22.
8. Dorheim, M. A.; Tracey, W. R.; Pollock, J. S.; Grammas, P. Nitric oxide synthase activity is elevated in brain microvessels in Alzheimert disease. Biochem. Biophys. Res. Commun. 1994, 205, 659-65.
9. Bhargava, H. N. Attenuation of tolerance to, and physical dependence on, morphine in the rat by inhibition of nitric oxide synthase. Gen. Pharmacol. 1995, 26, 1049-53.
10. Seo, H. G.; Takata, I.; Nakamura, M.; Tatsumi, H.; Suzuki, K.; Fujii, J.; Taniguchi, N. Induction of nitric oxide synthase and comcommitant suppression of superoxide dismutases in experimental colitis in rats. Arch. Biochem. Biophys. 1995, 324, 41-7.
11. Kubes, P.; Suzuki, M.; Granger, D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc. Nati. Acad. Sci. U.S.A. 1991, 88, 4651-5.
12. Marletta, M. A. Approaches toward selective inhibition of nitric oxide synthase. J. Med. Chem. 1994, 37, 1899-1907.
13. (a) Collins, J. L.; Shearer, B. G.; Oplinger, J. A.; Lee, S.; Garvey, E. P.; Salter, M.; Duffy, C.; Burnette, T. C.; Furfine, E. S. N-Phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: structure-activity studies and demonstration of in vivo activity. J. Med. Chem. 1998, 41, 2868-2871.
14. (b) Cowart, M.; Kowaluk, E. A.; Daanen, J. F.; Kohlhaas, K L.; Alexander, K M.; Wagenaar, F. L.; Kerwin, J. F., Jr. Nitroaromatic amino acids as inhibitors of neuronal nitric oxide synthase. J. Med. Chem. 1998, 41, 2636-2642.
15. Wright, C. W.; Rees, D. D.; Moncada, S. Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc. Res. 1992, 26, 48-57.
16. Hansen, D. W., Jr.; Peterson, K. B.; Trivedi, M.; Kramer, S. W.; Webber, B. K.; Tjoeng, F. S.; Moore, W. M.; Jerome, G. M.; Kornmeier, C. M.; Manning, P. T.; Connor, J. R.; Misko, T. P.; Currie, M. G.; Pitzele, B. S. 2-Iminohomopiperidineium salts as selective inhibitors of inducible nitric oxide synthase (iNOS). J. Med. Chem. 1999, 41, 1361-1366.
17. (b) Garvey, E. P.; Oplinger, J. A.; Furfine, E. S.; Kiff, R. J.; Laszlo, F.; Whittle, B. J. R.; Knowles, R. G. 1400W is a slow, tight binding, and highly selective inhibitor of inducible nitric oxide synthase in vitro and in vivo. J. Biol. Chem. 1997, 272, 4959-4963.
18. (c) Nakane, M.; Klinghofer, V.; Kuk, J. E.; Donnelly, J. L.; Budzik, G. P.; Pollock, J. S.; Basha, F.; Carter, G. W. Novel potent and selective inhibitors of inducible nitric oxide synthase. Mol. Pharmacol. 1995, 47, 831-834.
19. G-Methyl-L-arginine functions as an alternate substrate and mechanism-based inhibitor of nitric oxide synthase. Biochemistry 1993, 32, 9677-85.
20. G-nitroarginine. Biochemistry 1993, 32, 8512-17.
21. McCall, T. B.; Feelisch, M.; Palmer, R. M. J.; Moncada, S. Identification of Nδ-iminoethyl-L-ornithine as an irreversible inhibitor of nitric oxide synthase in phagocytic cells. Br. J. Pharmacol. 1991, 102, 234-8.
22. 5-(1-Imino-3-butenyl)-L-ornithine. A neuronal isoform selective mechanism-based inactivator of nitric oxide synthase. J. Biol. Chem. 1998, 273, 8882-8889.
23. G-propyl-L-arginine. J. Med. Chem. 1997, 40, 3869-70.
24. Narayanan, K.; Spack, L.; McMillan, K.; Kilbourn, R. G.; Hayward, M. A.; Masters, B. S. S.; Griffith, O. W. S-Alkyl-L-thiocitrullines. J. Biol. Chem. 1995, 270, 11103-10.
25. i values are a little different than those published: nNOS = 0.11 μM; iNOS = 80 μM; eNOS = 10 μM; selectivities are nNOS/iNOS = 727 and nNOS/eNOS = 91.
26. Wolff, D. J.; Lubeskie, A. Aminoguanidine is an isoform-selective, mechanism-based inactivater of nitric oxide synthase. Arch. Biochem. Biophys. 1995, 316, 290-301.
27. Garvey, E. P.; Oplinger, J.; Tanoury, G. J.; Sherman, P. A.; Fowler, M.; Marshall, S.; Harmon, M. F.; Paith, J. E.; Furfine, E. S. Potent and selective inhibition of human nitric oxide synthase. J. Biol. Chem. 1994, 269, 26669-26676.
28. Shearer, B. G.; Lee, S.; Oplinger, J. A.; Frick, L. W.; Garvey, E. P.; Furfine, E. S. Substituted N-phenylisothioureas: potent inhibitors of human nitric oxide synthase with neuronal isoform selectivity. J. Med. Chem. 1997, 40, 1901-05.
29. (a) Moore, W. M.; Webber, R. K.; Fok, K. F.; Jerome, G. M.; Conner, J. R.; Manning, P. T.; Wyatt, P. S.; Misko, T. P.; Tjoeng, F. S.; Currie, M. G. 2-Iminopiperidine and other 2-imonoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms. J. Med. Chem. 1996, 39, 669-672.
30. (b) Moore, W. M.; Webber, R. K.; Fok, K. F.; Jerome, G. M.; Kornmeier, C. M.; Tjoeng, F. S.; Currie, M. G. Inhibitors of human nitric oxide synthase isoforms with the carbamidine moiety as a common structural element. Bioorg. Med. Chem. 1996, 4, 1559-64.
31. Wolff, D. J.; Gribin, B. J. The inhibition of the constitutive and inducible nitric oxide synthase isoforms by indazole agents. Arch. Biochem. Biophys. 1994, 311, 300-306.
32. Hagen, T. J.; Bergmanis, A. A.; Kramer, S. W.; Fok, K. F.; Schmelzer, A. E.; Pitzele, B. S.; Swenton, L.; Jerome, G. M.; Kornmeier, C. M.; Moore, W. M.; Branson, L. F.; Conner, J. R.; Manning, P. T.; Currie, M. G.; Hallinan, E. A. 2-Iminopyrrolidines as potent and selective inhibitors of human inducible nitric oxide synthase. J. Med. Chem. 1998, 41, 3675-83.
33. G-nitro-L-arginine. Br. J. Pharmacol. 1991, 104, 31-38.
34. ω-nitroarginine- and phenylalanine-containing dipeptides and dipeptide esters. J. Med. Chem. 1997, 40, 2813-17.
35. Recently, we synthesized the N-acetylated N-terminal amine and found that it was a much poorer inhibitor of all of the isozymes (at least 200-fold; Huang, H., and Silverman, R. B., unpublished results). If steric hindrance is not a problem, then the electrostatic interaction shown in Figure 1 may be important.
36. Lukas, T. J.; Mirzoeva, S.; Slomczynska, U.; Watterson, D. M. Identification of novel classes of protein kinase inhibitors using combinatorial peptide chemistry based on functional genomics knowledge. J. Med. Chem. 1999, in press.
37. ε-tert-butyloxycarbonyl-L-lysine and W-benzyloxycarbonyl-Nε-tert-butyloxycarbonyl-L-lysine. Synth. Comm. 1981, 11, 303-314.
38. Tesser, G. I.; Schwyzer, R. Synthesis of 17, 18-diornithine-δ-corticotropin-(1-24)-tetracosapeptide, a biologically active analogue of adrenocorticotropic hormone. Helv. Chim. Acta 1966, 49, 1013-22.
39. Bodanszky, M.; Klausner, Y. S.; Mutt, V. Synthesis of the vasoactive intestinal peptide (VIP) I. the C-terminal cyanogen bromide fragment. Bioorg. Chem. 1972, 2, 30-38.
40. Hevel, J. M.; White, K. A.; Marietta, M. A. Purification of the inducible murine macrophage nitric oxide synthase. J. Biol. Chem. 1991, 266, 22789-91.
41. Roman, L. J.; Sheta, E. A.; Martasek, P.; Gross, S. S.; Liu, Q.; Masters, B. S. S. High-level expression of functional rat neuronal nitric oxide synthase in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 8428-32.
42. Gerber, N. C.; Montellano, P. R. Neuronal nitric oxide synthase: expression in Escherichia coli, irreversible inhibition by phenyldiazene, and active site topology. J. Biol. Chem. 1995, 270, 17791-96.
43. Martasek, P.; Liu, Q.; Roman, L. J.; Gross, S. S.; Sessa, W. C.; Masters, B. S. S. Characterization of bovine endothelial nitric oxide synthase expressed in Escherichia coli. Biochem. Biophys. Res. Commun. 1996, 219, 359-65.
44. G-Nitroarginine. Biochemistry 1993, 32, 8512-17.
45. Hevel, J. M.; Marietta, M. A. Nitric oxide synthase assays Methods Enzymol. 1994, 133, 250-8.
46. Dixon, M. The determination of enzyme inhibitor constants. Biochem. J. 1953, 55, 170-1.