Melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-Nïb modified at the para position of the benzyl side chain (DPhe): Importance for mouse melanocortin-3 receptor agonist versus antagonist activity

Journal of Medicinal Chemistry

Volumn 51, Issue 18, 2008, Pages 5585-5593

  Proneth, Bettina ^a   Pogozheva, Irina D ^b   Portillo, Federico P ^a   Mosberg, Henry I ^b   Haskell Luevano, Carrie ^a  

^a UNIVERSITY OF FLORIDA   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLHISTIDYL DEXTRO PHENYLALANYLARGINYLTRYPTOPHANAMIDE; ALPHA INTERMEDIN; BETA INTERMEDIN; HORMONE RECEPTOR STIMULATING AGENT; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 3 RECEPTOR STIMULATING AGENT; MELANOCORTIN 4 RECEPTOR; TETRAPEPTIDE AMIDE; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ARTICLE; CELL STRAIN HEK293; CONCENTRATION RESPONSE; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; REACTION ANALYSIS; RECEPTOR BLOCKING; STRUCTURE ACTIVITY RELATION;

ANIMALS; ELECTROSTATICS; MELANOCORTINS; MICE; RECEPTOR, MELANOCORTIN, TYPE 3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 52449094727     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm800291b     Document Type: Article

References (51)

1. Robbins, L. S.; Nadeau, J. H.; Johnson, K. R.; Kelly, M. A.; Roselli-Rehfuss, L.; et al. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function. Cell 1993, 72, 827-834.
2. Mountjoy, K. G.; Robbins, L. S.; Mortrud, M. T.; Cone, R. D. The cloning of a family of genes that encode the melanocortin receptors. Science 1992, 257, 1248-1251.
3. Valverde, P.; Healy, E.; Jackson, I.; Rees, J. L.; Thody, A. J. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nat. Genet. 1995, 11, 328-330.
4. Lu, D.; Willard, D.; Patel, I. R.; Kadwell, S.; Overton, L.; et al. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 1994, 371, 799-802.
5. Catania, A.; Airaghi, L.; Colombo, G.; Lipton, J. M. α-Melanocyte- stimulating hormone in normal human physiology and disease states. Trends Endocrinol. Metab. 2000, 11, 304-308.
6. Ni, X. P.; Bhargava, A.; Pearce, D.; Humphreys, M. H. Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2006, 290, R560-567.
7. Ni, X. P.; Pearce, D.; Butler, A. A.; Cone, R. D.; Humphreys, M. H. Genetic disruption of γ-melanocyte-stirnulating hormone signaling leads to salt-sensitive hypertension in the mouse. J. Clin. Invest. 2003, 111, 1251-1258.
8. Mayan, H.; Ni, X. P.; Almog, S.; Humphreys, M. H. Suppression of γ-melanocyte-stimulating hormone secretion is accompanied by salt-sensitive hypertension in the rat. Hypertension 2003, 42, 962-967.
9. Vaisse, C.; Clement, K.; Guy-Grand, B.; Froguel, P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat. Genet. 1998, 20, 113-114.
10. Yeo, G. S.; Farooqi, I. S.; Aminian, S.; Halsall, D. J.; Stanhope, R. G.; et al. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 1998, 20, 111-112.
11. Huszar, D.; Lynch, C. A.; Fairchild-Huntress, V.; Dunmore, J. H.; Fang, Q.; et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997, 88, 131-141.
12. Mains, R. E.; Eipper, B. A. Biosynthesis of adrenocorticotropic hormone in mouse pituitary tumor cells. J. Biol. Chem. 1976, 251, 4115-4120.
13. Eipper, B. A.; Mains, R. E. Structure and biosynthesis of proadrenocorticotropin/endorphin and related peptides. Endocr. Rev. 1980, 1, 1-27.
14. Castrucci, A. M.; Hadley, M. E.; Sawyer, T. K.; Wilkes, B. C.; al-Obeidi, F.; et al. α-melanotropin: the minimal active sequence in the lizard skin bioassay. Gen. Comp. Endrocrinol. 1989, 73, 157-163.
15. Hruby, V. J.; Wilkes, B. C.; Hadley, M. E.; Al-Obeidi, F.; Sawyer, T. K.; et al. α-Melanotropin: the minimal active sequence in the frog skin bioassay. J. Med. Chem. 1987, 30, 2126-2130.
16. Gantz, I.; Miwa, H.; Konda, Y.; Shimoto, Y.; Tashiro, T.; et al. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J. Biol. Chem. 1993, 268, 15174-15179.
17. Gantz, I.; Konda, Y.; Tashiro, T.; Shimoto, Y.; Miwa, H.; et al. Molecular cloning of a novel melanocortin receptor. J. Biol. Chem. 1993, 268, 8246-8250.
18. Mountjoy, K. G.; Mortrud, M. T.; Low, M. J.; Simerly, R. B.; Cone, R. D. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 1994, 8, 1298-1308.
19. Roselli-Rehfuss, L.; Mountjoy, K. G.; Robbins, L. S.; Mortrud, M. T.; Low, M. J.; et al. Identification of a receptor for γ melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 8856-8860.
20. Chen, A. S.; Marsh, D. J.; Trumbauer, M. E.; Frazier, E. G.; Guan, X. M.; et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 2000, 26, 97-102.
21. Butler, A. A.; Kesterson, R. A.; Khong, K.; Cullen, M. J.; Pelleymounter, M. A.; et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 2000, 141, 3518-3521.
22. Ballet, S.; Mayorov, A. V.; Cai, M.; Tymecka, D.; Chandler, K. B.; et al. Novel selective human melanocortin-3 receptor ligands: use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold. Bioorg. Med. Chem. Lett. 2007, 17, 2492-2498.
23. Grieco, P.; Balse, P. M.; Weinberg, D.; MacNeil, T.; Hruby, V. J. D-Amino acid scan of γ-melanocyte-stimulating hormone: importance of Trp(8) on human MC3 receptor selectivity. J. Med. Chem. 2000, 43, 4998-5002.
24. Mayorov, A. V.; Cai, M.; Chandler, K. B.; Petrov, R. R.; Van Scoy, A. R.; et al. Development of cyclic γ-MSH analogues with selective hMC3R agonist and hMC3R/hMC5R antagonist activities. J. Med. Chem. 2006, 49, 1946-1952.
25. Al-Obeidi, F.; Castrucci, A. M.; Hadley, M. E.; Hruby, V. J. Potent and prolonged acting cyclic lactam analogues of α-melanotropin: design based on molecular dynamics. J. Med. Chem. 1989, 32, 2555-2561.
26. Hruby, V. J.; Lu, D.; Sharma, S. D.; Castrucci, A. L.; Kesterson, R. A.; et al. Cyclic lactam α-melanotropin analogues of Ac-Nle4-cyclo[Asp5,D- Phe7,Lys10] α-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors. J. Med. Chem. 1995, 38, 3454-3461.
27. Haskell-Luevano, C.; Cone, R. D.; Monck, E. K.; Wan, Y. P. Structure activity studies of the melanocortin-4 receptor by in vitro mutagenesis: identification of agouti-related protein (AGRP), melanocortin agonist and synthetic peptide antagonist interaction determinants. Biochemistry 2001, 40, 6164-6179.
28. Holder, J. R.; Bauzo, R. M.; Xiang, Z.; Haskell-Luevano, C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH(2) at the mouse melanocortin receptors. Part 2. Modifications at the Phe position. J. Med. Chem. 2002, 45, 3073-3081.
29. Chen, M.; Aprahamian, C. J.; Celik, A.; Georgeson, K. E.; Garvey, W. T.; et al. Molecular characterization of human melanocortin-3 receptor ligand-receptor interaction. Biochemistry 2006, 45, 1128-1137.
30. Fleck, B. A.; Chen, C.; Yang, W.; Huntley, R.; Markison, S.; et al. Molecular interactions of nonpeptide agonists and antagonists with the melanocortin-4 receptor. Biochemistry 2005, 44, 14494-14508.
31. Haskell-Luevano, C. In vitro mutagenesis studies of melanocortin receptor coupling and ligand binding The Melanocortin Receptors; Humana Press: Totowa, NJ, 2000; pp 263-306.
32. Haskell-Luevano, C.; Sawyer, T. K.; Trumpp-Kallmeyer, S.; Bikker, J. A.; Humblet, C.; et al. Three-dimensional molecular models of the hMC1R melanocortin receptor: complexes with melanotropin peptide agonists. Drug Des. Discov. 1996, 14, 197-211.
33. Hogan, K.; Peluso, S.; Gould, S.; Parsons, I.; Ryan, D.; et al. Mapping the binding site of melanocortin 4 receptor agonists: a hydrophobic pocket formed by i3.28(125), i3.32(129), and i7.42(291) is critical for receptor activation. J. Med. Chem. 2006, 49, 911-922.
34. Nickolls, S. A.; Cismowski, M. I.; Wang, X.; Wolff, M.; Conlon, P. J.; et al. Molecular determinants of melanocortin 4 receptor ligand binding and MC4/MC3 receptor selectivity. J. Pharmacol. Exp. Ther. 2003, 304, 1217-1227.
35. Pogozheva, I. D.; Chai, B. X.; Lomize, A. L.; Fong, T. M.; Weinberg, D. H.; et al. Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists. Biochemistry 2005, 44, 11329-11341.
36. Yang, Y.; Dickinson, C.; Haskell-Luevano, C.; Gantz, I. Molecular basis for the interaction of [Nle4,D-Phe7]melanocyte stimulating hormone with the human melanocortin-1 receptor. J. Biol. Chem. 1997, 272, 23000-23010.
37. Yang, Y. K.; Fong, T. M.; Dickinson, C. J.; Mao, C.; Li, J. Y.; et al. Molecular determinants of ligand binding to the human melanocortin-4 receptor. Biochemistry 2000, 39, 14900-14911.
38. Danho, W.; Swistok, J.; Cheung, A. W.; Kurylko, G.; Franco, L.; et al. Structure-activity relationship of linear peptide Bu-His6-DPhe7-Arg8-Trp9-Gly10- NH2 at the human melanocortin-1 and -4 receptors: DPhe7 and Trp9 substitution. Bioorg. Med. Chem. Lett. 2003, 13, 649-652.
39. Cotton, F. A.; Wilkinson G. Advanced Inorganic Chemistry, 5th ed.; Wiley Interscience: New York, 1988.
40. McLachlan, A. D. Three-body dispersion forces. Mol. Phys. 1963, 6, 423-427.
41. Miller, K. J. Additivity methods in molecular polarizability. J. Am. Chem. Soc. 1990, 112, 8533-8542.
42. Carpino, L. A.; Han, G. Y. 9-Fluorenylmethoxycarbonyl amino-protecting group. J. Org. Chem. 1972, 37, 3404-3409.
43. Kaiser, E.; Colescott, R. L.; Bossinger, C. D.; Cook, P. I. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal. Biochem. 1970, 34, 595-598.
44. Chen, W.; Shields, T. S.; Stork, P. J.; Cone, R. D. A colorimetric assay for measuring activation of Gs- and Gq-coupled signaling pathways. Anal. Biochem. 1995, 226, 349-354.
45. Chen, C. A.; Okayama, H. Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with Plasmid DNA. Biotechniques 1988, 6, 632-638.
46. Holder, J. R.; Bauzo, R. M.; Xiang, Z.; Haskell-Luevano, C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH(2) at the mouse melanocortin receptors. 1. Modifications at the His position. J. Med. Chem. 2002, 45, 2801-2810.
47. Holder, J. R.; Xiang, Z.; Bauzo, R. M.; Haskell-Luevano, C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-D-Phe-Arg-Trp-NH2 at the mouse melanocortin receptors. 4. Modifications at the Trp position. J. Med. Chem. 2002, 45, 5736-5744.
48. Holder, J. R.; Xiang, Z.; Bauzo, R. M.; Haskell-Luevano, C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the mouse melanocortin receptors. Part 3: modifications at the Arg position. Peptides 2003, 24, 73-82.
49. Ott, R. L.; Longnecker, M. An Introduction to Statistical Methods and Data Analysis, 5th ed.; Duxbury: Pacific Grove, CA, 2001.
50. Schild, H. O. Pa, a new scale for the measurement of drug antagonism. Br. J. Pharmacol. Chemother. 1947, 2, 189-206.
51. Baker, N. A.; Sept, D.; Joseph, S.; Holst, M. J.; McCammon, J. A. Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 10037-10041.