Potent and selective agonists of human melanocortin receptor 5: Cyclic analogues of α-melanocyte-stimulating hormone

Journal of Medicinal Chemistry

Volumn 50, Issue 10, 2007, Pages 2520-2526

  Bednarek, Maria A ^a   MacNeil, Tanya ^a   Tang, Rui ^a   Fong, Tung M ^a   Cabello, M Angeles ^b   Maroto, Marta ^b   Teran, Ana ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Medical affairs Merck sharp and Dohme ltd   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLNORLEUCYLCYCLO(5 ASPARTYL 6 HISTIDYL 7 DEXTRO PHENYLALANYL 8 ARGINYLTRYPTOPHYLLYSINE)AMIDE; ACETYLNORLEUCYLCYCLO(ASPARTYLOCTAHYDROINDOLE 2 CARBOXYL DEXTRO 4,4' BIPHENYL 8 PIPECOLATE TRYPTOPHYLLYSINE)AMIDE; ALPHA INTERMEDIN; AMINO ACID; ARGININE; CYCLOPEPTIDE; HISTIDINE; MELANOCORTIN 1 RECEPTOR; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN 5 RECEPTOR; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; BINDING ASSAY; CHO CELL; CONTROLLED STUDY; FEMALE; HYDROPHOBICITY; NONHUMAN; STRUCTURE ANALYSIS;

ALPHA-MSH; ANIMALS; BINDING, COMPETITIVE; CHO CELLS; CRICETINAE; CRICETULUS; CYCLIC AMP; HUMANS; MELANOCYTE-STIMULATING HORMONES; PEPTIDES, CYCLIC; RADIOLIGAND ASSAY; RECEPTORS, CORTICOTROPIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34249093541     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0614275     Document Type: Article

References (47)

1. Bertagna, X. Proopiomelanocortin-derived peptides. Endocrinol. Metab. Clin. North Am. 1994, 23, 467-485.
2. Hadley, M. E. The Melanotropic Peptides: Source, Synthesis, Chemistry, Secretion, and Metabolism; CRC Press: Boca Raton, FL, 1989.
3. Buddgy, J. J. Binding of α-melanocyte-stimulating hormone to its G-protein-coupled receptor on B-lymphocytes activates the Jak/STAT pathway. Biochem. J. 1998, 331, 211-216.
4. MacNeil, D. J.; Howard, A. D.; Guan, X.; Fong, T. M.; Nargund, R. P.; Bednarek, M. A.; Goulet, M. T.; Weinberg, D. H.; Strack, A. M.; Marsh, D. J.; Chen, H. Y.; Shen, C.-P.; Chen, A. S.; Rosenblum, C. L.; MacNeil, T.; Tota, M.; MacIntyre, E. D.; Van der Ploeg, L. H. T. The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur. J. Pharmacol. 2002, 450, 93-109.
5. Tatro, J. B. Receptor biology of the melanocortins, a family of neuroimmunomodulatory peptides. Neuroimmunomodulation 1996, 3, 259-284.
6. Wikberg, J. E. S. Melanocortin receptors: perspectives for novel drugs. Eur. J. Pharmacol. 1999, 375, 295-310.
7. Wikberg, J. E. S. Melanocortin receptors: new opportunities in drug discovery. Exp. Opin. Ther. Patents 2001, 11, 61-76.
8. Starowicz, K.; Przewlocka, B. The role of melanocortins and their receptors in inflammatory processes, nerve regeneration and nociception. Life Sci. 2003, 73, 823-847.
9. Chhajlani, V. Distribution of cDNA of melanocortin receptor subtypes in human tissues. Biochem. Mol. Biol. Int. 1996, 38, 73-80.
10. Frandberg, P.-A.; Xu, X.; Chhajlani, V. Glutamine235 and Arginine272 in human melanocortin 5 receptor determines its low affinity to MSH. Biochem. Biophys. Res. Commun. 1997, 236, 489-492.
11. Schioth, H. B.; Fredriksson, A.; Carlsson, C.; Yook, P.; Muceniece, R.; Wikberg, J. E. S. Evidence indicating that the extracellular loops of the mouse MC5 receptor do not participate in ligand binding. Mol. Cell. Endocrinol. 1998, 39, 109-115.
12. i. Biochem. Biophys. Res. Commun. 2002, 290, 844-850.
13. Cone, R. D.; Lu, D.; Koppula, S.; Vage, D. I.; Klungland, H.; Boston, B.; Chen, W.; Orth, D. N.; Pouton, C.; Kesterson, R. A. The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation. Recent Prog. Horm. Res. 1996, 51, 287-318.
14. Fan, W.; Boston, B. A.; Kesterson, R. A.; Cone, R. D. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 1997, 385, 165-168.
15. Huszar, D.; Lynch, C. A.; Fairchild-Huntress, V.; Dunmore, J. H.; Fang, Q.; Berkemeier, L. R.; Gu, W.; Kesterson, R. A.; Boston, B. A.; Cone, R. D.; Smith, F. J.; Campfield, L. A.; Burn, P.; Lee, F. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997, 88, 131-141.
16. Chhajlani, V.; Muceniece, R.; Wikberg, J. E. S. Molecular cloning of a novel human melanocortin receptor. Biochem. Biophys. Res. Commun. 1993, 195, 866-873.
17. Barrett, P.; MacDonald, A.; Helliwell, R.; Davidson, G.; Morgan, P. Cloning and expression of a new member of the melanocyte-stimulating hormone receptor family. J. Mol. Endocrinol. 1994, 12, 203-213.
18. Akbulut, S.; Byersdorfer, A. A.; Larsen, C. P.; Zimmer, S. L.; Humphreys, T. D.; Clarke, B. L. Expression of the Melanocortin 5 Receptor on Rat Lymphocytes. Biochem. Biophys. Res. Commun. 2001, 281, 1086-1092.
19. Labbe, O.; Desarnaud, F.; Eggerickx, D.; Vassart, G.; Parmentier, M. Molecular Cloning of a Mouse Melanocortin 5 Receptor Gene Widely Expressed in Peripheral Tissues. Biochemistry 1994, 33, 4543-4549.
20. Griffon, N.; Mignon, V.; Facchinetti, P.; Diaz, J.; Schwartz, J.-Ch.; Sokoloff, P. Molecular cloning and characterization of the rat fifth melanocortin receptor. Biochem. Biophys. Res. Commun. 1994, 200, 1007-1014.
21. Gantz, I.; Shimoto, Y.; Konda, Y.; Miwa, H.; Dickinson, C. J.; Yamada, T. Molecular cloning, expression, and characterization of a fifth melanocortin receptor. Biochem. Biophys. Res. Commun. 1994, 200, 1214-1220.
22. Chen, W. The melanocortin-5 receptor. In The melanocortin receptors; Cone, R. D., Ed.; Humana Press: Totowa, NJ, 2000; pp 449-472.
23. Fathi, Z.; Iben, L. G.; Parker, E. M. Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. Neurochem. Res. 1995, 20, 107-113.
24. Zhang, L.; Antonavage, M.; Huang, Q.; Li, W.-H.; Eisinger, M. Proopiomelanocortin peptides and sebogenesis. Ann. N.Y. Acad. Sci. 2003, 994, 154-161.
25. Van der Kraan, M.; Adan, R. A.; Entwistle, M. L.; Gispen, W. H.; Burbach, J. P.; Tatro, J. B. Expression of melanocortin-5 receptor in secretory epithelia supports a functional role in exocrine and endocrine glands. Endocrinology 1998, 139, 2348-2355.
26. Chen, W.; Kelline, M. A.; Opitz-Araya, X.; Thomas, R. E.; Low, M. J.; Cone, R. D. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 1997, 91, 789-798.
27. Murray, J. F.; Adan, R. A.; Walker, R.; Baker, B. I.; Thody, A. J.; Nijenhuis, W. A.; Yukitake, J.; Wilson, C. A. Melanin-concentrating hormone, melanocortin receptors and regulation of luteinizing hormone release. J. Neuroendocrinol. 2000, 12, 217-223.
28. Butler, A. A.; Cone, R. D. The melanocortin receptors: lessons from knockout models. Neuropeptides 2002, 36, 77-84.
29. Caldwell, H. K.; Lepri, J. J. Disruption of the fifth melanocortin receptor alters the urinary excretion of aggression-modifying phermones in male house mice. Chem. Senses 2002, 27, 91-94.
30. Morgan, C.; Thomas, R. E.; Cone, R. D. Melanocortin-5 receptor deficiency promotes defensive behavior in male mice. Horm. Behav. 2004, 45, 58-63.
31. Chagnon, Y. C.; Chen, W. J.; Perusse, L.; Chagnon, M.; Nadeau, A.; Wilkison, W. O.; Bouchard, C. Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Quebec family study. Mol. Med. 1997, 3, 663-673.
32. 7]-α- melanocyte stimulating hormone: A highly potent α-melanotropin with ultralong biological activity. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 5854-5758.
33. Al-Obeidi, F.; de L. 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.
34. 2 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.
35. Cai, M.; Cai, C.; Mayorov, A. V.; Xiong, C.; Cabello, C. M.; Soloshonok, V. A.; Swift, J. R.; Trivedi, D.; Hruby, V. J. Biological and conformational study of β-substituted prolines in MT-II template: steric effects leading to human MC5 receptor selectivity. J. Pept. Res. 2004, 63, 116-131.
36. Balse-Srinivasan, P.; Grieco, P.; Cai, M.; Trivedi, D.; Hruby, V. J. Structure-activity relationships of novel cyclic α-MSH/β-MSH hybrid analogs that lead to potent and selective ligands for human MC3R and human MC5R. J. Med. Chem. 2003, 46, 3728-3733.
37. Balse-Srinivasan, P.; Grieco, P.; Cai, M.; Trivedi, D.; Hruby, V. J. Structure-activity relationships of γ-MSH analogues at the human melanocortin MC3, MC4, and MC5 receptors. Discovery of highly selective hMC3R, hMC4R, and hMC5R analogues. J. Med. Chem. 2003, 46, 4965-4973.
38. 2 tetrapeptides at the melanocortin receptors. Eur. J. Pharmacol. 2003, 462, 41-52.
39. Bednarek, M. A.; Silva, M. V.; Arison, B.; MacNeil, T.; Kalyani, R. N.; Huang, R-R. C.; Weinberg, D. H. Structure-function studies on the cyclic peptide MT-II, lactam derivative of α-melanotropin. Peptides 1999, 20, 401-409.
40. Bednarek, M. A.; MacNeil, T.; Kalyani, R. N.; Tang, R.; Van der Ploeg, L. H. T.; Weinberg, D. H. Analogs of MTII, lactam derivatives of α-melanotropin, modified at the N-terminus, and their selectivity at human melanocortin receptors 3, 4 and 5. Biochem. Biophys. Res. Commun. 1999, 261, 209-213.
41. Bednarek, M. A.; MacNeil, T.; Kalyani, R. N.; Tang, R.; Van der Ploeg, L. H. T.; Weinberg, D. H. Analogs of lactam derivatives of α-melanotropin with basic and acidic residues. Biochem. Biophys. Res. Commun. 2000, 272, 23-28.
42. Tan, C. P.; McKee, K. K.; Weinberg, D. H.; MacNeil, T.; Palyha, O. C.; Feighner, D. D.; Hreniuk, D. L.; Van der Ploeg, L. H. T.; MacNeil, D. J.; Howard, A. D. Molecular analysis of a new splice variant of the human melanocortin-1 receptor. FEBS Lett. 1999, 451, 137-141.
43. Grieco, P.; Balse-Srinivasan, P.; Han, G.; Weinberg, D.; MacNeil, T.; Van der Ploeg, L. H. T.; Hruby, V. J. Extensive structure-activity studies of lactam derivatives of MT-II and SHU-9119: Their activity and selectivity at human melanocortin receptors 3, 4, and 5. J. Pept. Res. 2003, 62, 199-206.
44. Prusis, P.; Muceniece, R.; Mutule, I.; Mutulis, F.; Wikberg, J. E. S. Design of new small cyclic melanocortin receptor-binding peptides using molecular modeling: role of the His residue in the melanocortin peptide core. Eur. J. Med. Chem. 2001, 36, 137-146.
45. 2 at the human melanocortin-1 and - 4 receptors: His6 substitution. Bioorg. Med. Chem. Let. 2003, 13, 1307-1311.
46. 2 at the Mouse Melanocortin Receptors. I. Modifications at the His Position. J. Med. Chem. 2002, 45, 2801-2810.
47. 2 at the human melanocortin-1 and -4 receptors: histidine substitution. Bioorg. Med. Chem. Let. 2003, 13, 133-137.