Design, synthesis, structural and functional characterization of novel melanocortin agonists based on the cyclotide kalata B1

Journal of Biological Chemistry

Volumn 287, Issue 48, 2012, Pages 40493-40501

  Eliasen, Rasmus ^a,d   Daly, Norelle L ^b,c   Wulff, Birgitte S ^a   Andresen, Thomas L ^d   Conde Frieboes, Kilian W ^a   Craik, David J ^c  

^a NOVO NORDISK A S   (Denmark)

^b JAMES COOK UNIVERSITY   (Australia)

^c UNIVERSITY OF QUEENSLAND   (Australia)

^d TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVE PEPTIDES; BACKBONE CYCLIZATION; CURRENT TREATMENTS; CYCLOTIDES; ENERGY EXPENDITURE; FUNCTIONAL ACTIVITIES; FUNCTIONAL CHARACTERIZATION; KALATA B1; NMR CHEMICAL SHIFTS; PEPTIDE CHEMISTRIES; RECEPTOR BINDING; THIOESTERS;

LEAD COMPOUNDS; MEDICAL PROBLEMS; NUTRITION; SCAFFOLDS;

PEPTIDES;

ALPHA INTERMEDIN; CYCLOTIDE; KALABATA B1; MELANOCORTIN 1 RECEPTOR; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN 5 RECEPTOR; MELANOCORTIN RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CYCLIZATION; DRUG DESIGN; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; PEPTIDE SYNTHESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN STABILITY;

AMINO ACID SEQUENCE; ANIMALS; CELL LINE; CRICETINAE; CRYSTALLOGRAPHY, X-RAY; CYCLOTIDES; DRUG DESIGN; KINETICS; MELANOCORTINS; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; RECEPTORS, MELANOCORTIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84870003472     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.395442     Document Type: Article

References (62)

1. Finucane, M. M., Stevens, G. A., Cowan, M. J., Danaei, G., Lin, J. K., Paciorek, C. J., Singh, G. M., Gutierrez, H. R., Lu, Y., Bahalim, A. N., Farzadfar, F., Riley, L. M., and Ezzati, M. (2011) National, regional, and global trends in body-mass index since 1980. Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377, 557-567
2. Stevens, J., Couper, D., Pankow, J., Folsom, A. R., Duncan, B. B., Nieto, F. J., Jones, D., and Tyroler, H. A. (2001) Sensitivity and specificity of anthropometrics for the prediction of diabetes in a biracial cohort. Obes. Res. 9, 696-705 (Pubitemid 33603884)
3. Wannamethee, S. G., Shaper, A. G., Durrington, P. N., and Perry, I. J. (1998) Hypertension, serum insulin, obesity, and the metabolic syndrome. J. Hum. Hypertens. 12, 735-741 (Pubitemid 28515605)
4. Wolf, H. K., Tuomilehto, J., Kuulasmaa, K., Domarkiene, S., Cepaitis, Z., Molarius, A., Sans, S., Dobson, A., Keil, U., and Rywik, S. (1997) Blood pressure levels in the 41 populations of the WHO MONICA Project. J. Hum. Hypertens. 11, 733-742 (Pubitemid 27503986)
5. Miller, W. C., Koceja, D. M., and Hamilton, E. J. (1997) A meta-analysis of the past 25 years of weight loss research using diet, exercise, or diet plus exercise intervention. Int. J. Obes. Relat. Metab. Disord. 21, 941-947 (Pubitemid 27427485)
6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285, 2486-2497
7. Wright, S. M., and Aronne, L. J. (2011) Obesity in 2010. The future of obesity medicine. Where do we go from here? Nat. Rev. Endocrinol. 7, 69-70
8. Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., and Cone, R. D. (1992) The cloning of a family of genes that encode the melanocortin receptors. Science 257, 1248-1251
9. Chhajlani, V., and Wikberg, J. E. (1992) Molecular cloning and expression of the human melanocyte-stimulating hormone receptor cDNA. FEBS Lett. 309, 417-420
10. Gantz, I., Konda, Y., Tashiro, T., Shimoto, Y., Miwa, H., Munzert, G., Watson, S. J., DelValle, J., and Yamada, T. (1993) Molecular cloning of a novel melanocortin receptor. J. Biol. Chem. 268, 8246-8250 (Pubitemid 23120413)
11. Gantz, I., Miwa, H., Konda, Y., Shimoto, Y., Tashiro, T., Watson, S. J., DelValle, J., and Yamada, T. (1993) Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J. Biol. Chem. 268, 15174-15179 (Pubitemid 23206671)
12. Chhajlani, V., Muceniece, R., and Wikberg, J. E. (1993) Molecular cloning of a novel human melanocortin receptor. Biochem. Biophys. Res. Commun. 195, 866-873 (Pubitemid 23280496)
13. Roselli-Rehfuss, L., Mountjoy, K. G., Robbins, L. S., Mortrud, M. T., Low, M. J., Tatro, J. B., Entwistle, M. L., Simerly, R. B., and Cone, R. D. (1993) Identification of a receptor for γ-melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc. Natl. Acad. Sci. U.S.A. 90, 8856-8860 (Pubitemid 23306409)
14. Mountjoy, K. G., Mortrud, M. T., Low, M. J., Simerly, R. B., and Cone, R. D. (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8, 1298-1308 (Pubitemid 24335073)
15. Starowicz, K., Bilecki, W., Sieja, A., Przewlocka, B., and Przewlocki, R. (2004) Melanocortin 4 receptor is expressed in the dorsal root ganglions and down-regulated in neuropathic rats. Neurosci. Lett. 358, 79-82 (Pubitemid 38340725)
16. Chen, A. S., Metzger, J. M., Trumbauer, M. E., Guan, X. M., Yu, H., Frazier, E. G., Marsh, D. J., Forrest, M. J., Gopal-Truter, S., Fisher, J., Camacho, R. E., Strack, A. M., Mellin, T. N., MacIntyre, D. E., Chen, H. Y., and Van der Ploeg, L. H. (2000) Role of the melanocortin-4 receptor in metabolic rate and food intake in mice. Transgenic Res. 9, 145-154 (Pubitemid 30610232)
17. Chen, W., Kelly, M. A., Opitz-Araya, X., Thomas, R. E., Low, M. J., and Cone, R. D. (1997) Exocrine gland dysfunction in MC5-R-deficient mice. Evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 91, 789-798 (Pubitemid 28007735)
18. Fathi, Z., Iben, L. G., and Parker, E. M. (1995) Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. Neurochem. Res. 20, 107-113
19. Hruby, V. J., Wilkes, B. C., Hadley, M. E., Al-Obeidi, F., Sawyer, T. K., Staples, D. J., de Vaux, A. E., Dym, O., Castrucci, A. M., and Hintz, M. F. (1987) α-Melanotropin. The minimal active sequence in the frog skin bioassay. J. Med. Chem. 30, 2126-2130 (Pubitemid 18046075)
20. Sawyer, T. K., Sanfilippo, P. J., Hruby, V. J., Engel, M. H., Heward, C. B., Burnett, J. B., and Hadley, M. E. (1980) 4-Norleucine, 7-D-phenylalanine- α-melanocyte-stimulating hormone. A highly potent α-melanotropin with ultralong biological activity. Proc. Natl. Acad. Sci. U.S.A. 77, 5754-5758 (Pubitemid 11206397)
21. Haskell-Luevano, C., Holder, J. R., Monck, E. K., and Bauzo, R. M. (2001) Characterization of melanocortin NDP-MSH agonist peptide fragments at the mouse central and peripheral melanocortin receptors. J. Med. Chem. 44, 2247-2252 (Pubitemid 32861783)
22. Wilczynski, A., Wang, X. S., Joseph, C. G., Xiang, Z., Bauzo, R. M., Scott, J. W., Sorensen, N. B., Shaw, A. M., Millard, W. J., Richards, N. G., and Haskell-Luevano, C. (2004) Identification of putative agouti-related protein(87-132)-melanocortin-4 receptor interactions by homology molecular modeling and validation using chimeric peptide ligands. J. Med. Chem. 47, 2194-2207 (Pubitemid 38478843)
23. He, S., Ye, Z., Dobbelaar, P. H., Bakshi, R. K., Hong, Q., Dellureficio, J. P., Sebhat, I. K., Guo, L., Liu, J., Jian, T., Lai, Y., Franklin, C. L., Reibarkh, M., Holmes, M. A., Weinberg, D. H., MacNeil, T., Tang, R., Tamvakopoulos, C., Peng, Q., Miller, R. R., Stearns, R. A., Chen, H. Y., Chen, A. S., Strack, A. M., Fong, T. M., Wyvratt, M. J., Jr., and Nargund, R. P. (2010) Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me- 1,2,4-triazole privileged structures for the treatment of obesity. Bioorg. Med. Chem. Lett. 20, 6524-6565
24. Emmerson, P. J., Fisher, M. J., Yan, L. Z., and Mayer, J. P. (2007) Melanocortin- 4 receptor agonists for the treatment of obesity. Curr. Top. Med. Chem. 7, 1121-1130 (Pubitemid 47044742)
25. Gustafson, K. R., Sowder, R. C., Henderson, L. E., Parsons, I. C., Kashman, Y., Cardellina, J. H., McMahon, J. B., Buckheit, R. W., Pannell, L. K., and Boyd, M. R. (1994) Circulins A and B. Novel human immunodeficiency virus (HIV)-inhibitory macrocyclic peptides from the tropical tree Chassalia parvifolia. J. Am. Chem. Soc. 116, 9337-9338
26. Saether, O., Craik, D. J., Campbell, I. D., Sletten, K., Juul, J., and Norman, D. G. (1995) Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1. Biochemistry 34, 4147-4158
27. Schöpke, T., Hasan Agha, M. I., Kraft, R., Otto, A., and Hiller, K. (1993) Hämtisch aktive komponenten aus Viola tricolor L. und Viola arvenses Murray. Sci. Pharm. 61, 145-153
28. Witherup, K. M., Bogusky, M. J., Anderson, P. S., Ramjit, H., Ransom, R. W., Wood, T., and Sardana, M. (1994) Cyclopsychotride A, a biologically active, 31-residue cyclic peptide isolated from Psychotria longipes. J. Nat. Prod. 57, 1619-1625
29. Gran, L. (1973) Oxytocic principles of Oldenlandia affinis. Lloydia 36, 174-178
30. Tam, J. P., Lu, Y. A., Yang, J. L., and Chiu, K. W. (1999) An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine- knot disulfides. Proc. Natl. Acad. Sci. U.S.A. 96, 8913-8918 (Pubitemid 29374682)
31. Lindholm, P., Göransson, U., Johansson, S., Claeson, P., Gullbo, J., Larsson, R., Bohlin, L., and Backlund, A. (2002) Cyclotides. A novel type of cytotoxic agents. Mol. Cancer Ther. 1, 365-369
32. Craik, D. J., Mylne, J. S., and Daly, N. L. (2010) Cyclotides. Macrocyclic peptides with applications in drug design and agriculture. Cell. Mol. Life Sci. 67, 9-16
33. Jennings, C., West, J., Waine, C., Craik, D., and Anderson, M. (2001) Biosynthesis and insecticidal properties of plant cyclotides. The cyclic knotted proteins from Oldenlandia affinis. Proc. Natl. Acad. Sci. U.S.A. 98, 10614-10619 (Pubitemid 32878669)
34. Claeson, P., Göransson, U., Johansson, S., Luijendijk, T., and Bohlin, L. (1998) Fractionation protocol for the isolation of polypeptides from plant biomass. J. Nat. Prod. 61, 77-81 (Pubitemid 28086978)
35. Craik, D. J., Daly, N. L., Bond, T., and Waine, C. (1999) Plant cyclotides. A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J. Mol. Biol. 294, 1327-1336 (Pubitemid 30008803)
36. Göransson, U., Luijendijk, T., Johansson, S., Bohlin, L., and Claeson, P. (1999) Seven novel macrocyclic polypeptides from Viola arvensis. J. Nat. Prod. 62, 283-286 (Pubitemid 29137907)
37. Gruber, C. W., Elliott, A. G., Ireland, D. C., Delprete, P. G., Dessein, S., Göransson, U., Trabi, M., Wang, C. K., Kinghorn, A. B., Robbrecht, E., and Craik, D. J. (2008) Distribution and evolution of circular miniproteins in flowering plants. Plant Cell 20, 2471-2483 (Pubitemid 352844612)
38. Hernandez, J. F., Gagnon, J., Chiche, L., Nguyen, T. M., Andrieu, J. P., Heitz, A., Trinh Hong, T., Pham, T. T., and Le Nguyen, D. (2000) Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure. Biochemistry 39, 5722-5730 (Pubitemid 30307960)
39. Wang, C. K., Kaas, Q., Chiche, L., and Craik, D. J. (2008) CyBase. A database of cyclic protein sequences and structures, with applications in protein discovery and engineering. Nucleic Acids Res. 36, D206-D210 (Pubitemid 351149723)
40. Colgrave, M. L., and Craik, D. J. (2004) Thermal, chemical, and enzymatic stability of the cyclotide kalata B1. The importance of the cyclic cystine knot. Biochemistry 43, 5965-5975 (Pubitemid 38669464)
41. Craik, D. J., Daly, N. L., and Waine, C. (2001) The cystine knot motif in toxins and implications for drug design. Toxicon 39, 43-60
42. Daly, N. L., Love, S., Alewood, P. F., and Craik, D. J. (1999) Chemical synthesis and folding pathways of large cyclic polypeptides. Studies of the cystine knot polypeptide kalata B1. Biochemistry 38, 10606-10614
43. Jagadish, K., and Camarero, J. A. (2010) Cyclotides, a promising molecular scaffold for peptide-based therapeutics. Biopolymers 94, 611-616
44. Clark, R. J., Daly, N. L., and Craik, D. J. (2006) Structural plasticity of the cyclic cystine-knot framework. Implications for biological activity and drug design. Biochem. J. 394, 85-93 (Pubitemid 43259658)
45. Gunasekera, S., Foley, F. M., Clark, R. J., Sando, L., Fabri, L. J., Craik, D. J., and Daly, N. L. (2008) Engineering stabilized vascular endothelial growth factor-A antagonists: synthesis, structural characterization, and bioactivity of grafted analogues of cyclotides. J. Med. Chem. 51, 7697-7704
46. Wong, C. T., Rowlands, D. K., Wong, C. H., Lo, T. W., Nguyen, G. K., Li, H. Y., and Tam, J. P. (2012) Orally active peptidic bradykinin B1 receptor antagonists engineered from a cyclotide scaffold for inflammatory pain treatment. Angew. Chem. Int. Ed. Engl. 51, 5620-5624
47. Thongyoo, P., Roqué-Rosell, N., Leatherbarrow, R. J., and Tate, E. W. (2008) Chemical and biomimetic total syntheses of natural and engineered MCoTI cyclotides. Org. Biomol. Chem. 6, 1462-1470 (Pubitemid 351469865)
48. Chan, L. Y., Gunasekera, S., Henriques, S. T., Worth, N. F., Le, S. J., Clark, R. J., Campbell, J. H., Craik, D. J., and Daly, N. L. (2011) Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds. Blood 118, 6709-6717
49. Reiss, S., Sieber, M., Oberle, V., Wentzel, A., Spangenberg, P., Claus, R., Kolmar, H., and Lösche, W. (2006) Inhibition of platelet aggregation by grafting RGD and KGD sequences on the structural scaffold of small disulfide- rich proteins. Platelets 17, 153-157 (Pubitemid 43791626)
50. Dawson, P. E., Muir, T. W., Clark-Lewis, I., and Kent, S. B. (1994) Synthesis of proteins by native chemical ligation. Science 266, 776-779 (Pubitemid 24359280)
51. Fujinari, E. M., and Courthaudon, L. O. (1992) Nitrogen-specific liquid chromatography detector based on chemiluminescence. Application to the analysis of ammonium nitrogen in waste water. J. Chromatogr. A 592, 209-214
52. Millard, E. L., Nevin, S. T., Loughnan, M. L., Nicke, A., Clark, R. J., Alewood, P. F., Lewis, R. J., Adams, D. J., Craik, D. J., and Daly, N. L. (2009) Inhibition of neuronal nicotinic acetylcholine receptor subtypes by α-conotoxin GID and analogues. J. Biol. Chem. 284, 4944-4951
53. Hutchinson, E. G., and Thornton, J. M. (1996) PROMOTIF. A program to identify and analyze structural motifs in proteins. Protein Sci. 5, 212-220 (Pubitemid 26054277)
54. Koradi, R., Billeter, M., and Wüthrich, K. (1996) MOLMOL. A program for display and analysis of macromolecular structures. J. Mol. Graph. 14, 29-32
55. DeLano, W. (2002) The PyMOL Molecular Graphics System. DeLano Scientific, San Carlos, CA
56. Conde-Frieboes, K., Thøgersen, H., Lau, J. F., Sensfuss, U., Hansen, T. K., Christensen, L., Spetzler, J., Olsen, H. B., Nilsson, C., Raun, K., Dahl, K., Hansen, B. S., and Wulff, B. S. (2012) Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R)-selective α-melanocyte-stimulating hormone (α-MSH) analogues. J. Med. Chem. 55, 1969-1977
57. Barry, D. G., Daly, N. L., Clark, R. J., Sando, L., and Craik, D. J. (2003) Linearization of a naturally occurring circular protein maintains structure but eliminates hemolytic activity. Biochemistry 42, 6688-6695 (Pubitemid 36666109)
58. Skjeldal, L., Gran, L., Sletten, K., and Volkman, B. F. (2002) Refined structure and metal-binding site of the kalata B1 peptide. Arch. Biochem. Biophys. 399, 142-148 (Pubitemid 34848600)
59. Castrucci, A. M., Hadley, M. E., Sawyer, T. K., and Hruby, V. J. (1984) Enzymological studies of melanotropins. Comp. Biochem. Physiol. B 78, 519-524
60. Werle, M., Schmitz, T., Huang, H. L., Wentzel, A., Kolmar, H., and Bernkop-Schnürch, A. (2006) The potential of cystine-knot microproteins as novel pharmacophoric scaffolds in oral peptide drug delivery. J. Drug Target. 14, 137-146 (Pubitemid 43878822)
61. Daly, N. L., Rosengren, K. J., and Craik, D. J. (2009) Discovery, structure, and biological activities of cyclotides. Adv. Drug Deliv. Rev. 61, 918-930
62. Rosengren, K. J., Daly, N. L., Plan, M. R., Waine, C., and Craik, D. J. (2003) Twists, knots, and rings in proteins. Structural definition of the cyclotide framework. J. Biol. Chem. 278, 8606-8616 (Pubitemid 36800615)