Rational design of a low molecular weight, stable, potent, and long-lasting GPR103 Aza-β3-pseudopeptide agonist

Journal of Medicinal Chemistry

Volumn 55, Issue 17, 2012, Pages 7516-7524

  Neveu, Cindy ^a   Lefranc, Benjamin ^b   Tasseau, Olivier ^c   Do Rego, Jean Claude ^a   Bourmaud, Adèle ^b   Chan, Philippe ^b   Bauchat, Patrick ^c   Marec, Olivier Le ^a   Chuquet, Julien ^a   Guilhaudis, Laure ^b   Boutin, Jean A ^d   Ségalas Milazzo, Isabelle ^b   Costentin, Jean ^a   Vaudry, Hubert ^a,b   Baudy Floc'H, Michèle ^c   Vaudry, David ^a,b   Leprince, Jérôme ^a,b  

^a UNIVERSITY OF ROUEN   (France)

^b UNIVERSITÉ DE ROUEN   (France)

^c UNIVERSITÉ DE RENNES 1   (France)

^d INSTITUT DE RECHERCHES SERVIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

26RFA[20-26] PSEUDOPEPTIDE AGONIST; AMINO ACID DERIVATIVE; CALCIUM ION; G PROTEIN COUPLED RECEPTOR; GPR103 PROTEIN; HYDROGEN; LV 2002; LV 2021; LV 2043; LV 2044; LV 2045; LV 2046; LV 2047; LV 2048; LV 2111; LV 2152; LV 2153; LV 2154; LV 2155; LV 2156; LV 2157; LV 2158; LV 2159; LV 2160; LV 2161; LV 2162; LV 2163; LV 2165; LV 2166; LV 2167; LV 2168; LV 2169; LV 2171; LV 2172; PEPTIDE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; APPETITE; ARTICLE; BINDING AFFINITY; BLOOD BRAIN BARRIER; CALCIUM MOBILIZATION; CONTROLLED STUDY; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG POTENCY; DRUG STABILITY; DRUG SYNTHESIS; FOOD INTAKE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; IN VITRO STUDY; IN VIVO STUDY; MALE; MOLECULAR WEIGHT; MOUSE; NONHUMAN; SERUM; STRUCTURE ACTIVITY RELATION;

ANIMALS; AZA COMPOUNDS; CIRCULAR DICHROISM; DRUG DESIGN; DRUG STABILITY; FEEDING BEHAVIOR; HYDROGEN BONDING; INJECTIONS, INTRAVENTRICULAR; MALE; MICE; MOLECULAR WEIGHT; PEPTIDES; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84866334829     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300507d     Document Type: Article

References (64)

1. Chartrel, N., Tsutsui, K., Costentin, J., and Vaudry, H. The RFamide-related peptides. In Handbook of Biologically Active Peptides; Kastin, A. J., Ed.; Elsevier: New York, 2006; pp 779-786.
2. Yang, H. Y.; Fratta, W.; Majane, E. A.; Costa, E. Isolation, sequencing, synthesis, and pharmacological characterization of two brain neuropeptides that modulate the action of morphine Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 7757-61 (Pubitemid 16204428)
3. Hinuma, S.; Habata, Y.; Fujii, R.; Kawamata, Y.; Hosoya, M.; Fukusumi, S.; Kitada, C.; Masuo, Y.; Asano, T.; Matsumoto, H.; Sekiguchi, M.; Kurokawa, T.; Nishimura, O.; Onda, H.; Fujino, M. A prolactin-releasing peptide in the brain Nature 1998, 393, 272-6 (Pubitemid 28261727)
4. Hinuma, S.; Shintani, Y.; Fukusumi, S.; Iijima, N.; Matsumoto, Y.; Hosoya, M.; Fujii, R.; Watanabe, T.; Kikuchi, K.; Terao, Y.; Yano, T.; Yamamoto, T.; Kawamata, Y.; Habata, Y.; Asada, M.; Kitada, C.; Kurokawa, T.; Onda, H.; Nishimura, O.; Tanaka, M.; Ibata, Y.; Fujino, M. New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals Nat. Cell Biol. 2000, 2, 703-8
5. Kotani, M.; Detheux, M.; Vandenbogaerde, A.; Communi, D.; Vanderwinden, J. M.; Le Poul, E.; Brezillon, S.; Tyldesley, R.; Suarez-Huerta, N.; Vandeput, F.; Blanpain, C.; Schiffmann, S. N.; Vassart, G.; Parmentier, M. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54 J. Biol. Chem. 2001, 276, 34631-6
6. Ohtaki, T.; Shintani, Y.; Honda, S.; Matsumoto, H.; Hori, A.; Kanehashi, K.; Terao, Y.; Kumano, S.; Takatsu, Y.; Masuda, Y.; Ishibashi, Y.; Watanabe, T.; Asada, M.; Yamada, T.; Suenaga, M.; Kitada, C.; Usuki, S.; Kurokawa, T.; Onda, H.; Nishimura, O.; Fujino, M. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor Nature 2001, 411, 613-7 (Pubitemid 32531412)
7. Chartrel, N.; Dujardin, C.; Anouar, Y.; Leprince, J.; Decker, A.; Clerens, S.; Do-Rego, J. C.; Vandesande, F.; Llorens-Cortes, C.; Costentin, J.; Beauvillain, J. C.; Vaudry, H. Identification of 26RFa, a hypothalamic neuropeptide of the RFamide peptide family with orexigenic activity Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 15247-52 (Pubitemid 37518047)
8. Fukusumi, S.; Yoshida, H.; Fujii, R.; Maruyama, M.; Komatsu, H.; Habata, Y.; Shintani, Y.; Hinuma, S.; Fujino, M. A new peptidic ligand and its receptor regulating adrenal function in rats J. Biol. Chem. 2003, 278, 46387-95 (Pubitemid 37452209)
9. Jiang, Y.; Luo, L.; Gustafson, E. L.; Yadav, D.; Laverty, M.; Murgolo, N.; Vassileva, G.; Zeng, M.; Laz, T. M.; Behan, J.; Qiu, P.; Wang, L.; Wang, S.; Bayne, M.; Greene, J.; Monsma, F., Jr.; Zhang, F. L. Identification and characterization of a novel RF-amide peptide ligand for orphan G-protein-coupled receptor SP9155 J. Biol. Chem. 2003, 278, 27652-7 (Pubitemid 36899952)
10. Ukena, K.; Tachibana, T.; Iwakoshi-Ukena, E.; Saito, Y.; Minakata, H.; Kawaguchi, R.; Osugi, T.; Tobari, Y.; Leprince, J.; Vaudry, H.; Tsutsui, K. Identification, localization, and function of a novel avian hypothalamic neuropeptide, 26RFa, and its cognate receptor, G protein-coupled receptor-103 Endocrinology 2010, 151, 2255-64
11. Bruzzone, F.; Lectez, B.; Tollemer, H.; Leprince, J.; Dujardin, C.; Rachidi, W.; Chatenet, D.; Baroncini, M.; Beauvillain, J. C.; Vallarino, M.; Vaudry, H.; Chartrel, N. Anatomical distribution and biochemical characterization of the novel RFamide peptide 26RFa in the human hypothalamus and spinal cord J. Neurochem. 2006, 99, 616-27 (Pubitemid 44477216)
12. Takayasu, S.; Sakurai, T.; Iwasaki, S.; Teranishi, H.; Yamanaka, A.; Williams, S. C.; Iguchi, H.; Kawasawa, Y. I.; Ikeda, Y.; Sakakibara, I.; Ohno, K.; Ioka, R. X.; Murakami, S.; Dohmae, N.; Xie, J.; Suda, T.; Motoike, T.; Ohuchi, T.; Yanagisawa, M.; Sakai, J. A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 7438-43 (Pubitemid 43727851)
13. Bruzzone, F.; Lectez, B.; Alexandre, D.; Jegou, S.; Mounien, L.; Tollemer, H.; Chatenet, D.; Leprince, J.; Vallarino, M.; Vaudry, H.; Chartrel, N. Distribution of 26RFa binding sites and GPR103 mRNA in the central nervous system of the rat J. Comp. Neurol. 2007, 503, 573-91 (Pubitemid 47051368)
14. Kampe, J.; Wiedmer, P.; Pfluger, P. T.; Castaneda, T. R.; Burget, L.; Mondala, H.; Kerr, J.; Liaw, C.; Oldfield, B. J.; Tschop, M. H.; Bagnol, D. Effect of central administration of QRFP(26) peptide on energy balance and characterization of a second QRFP receptor in rat Brain Res. 2006, 1119, 133-49 (Pubitemid 44647238)
15. do Rego, J. C.; Leprince, J.; Chartrel, N.; Vaudry, H.; Costentin, J. Behavioral effects of 26RFamide and related peptides Peptides 2006, 27, 2715-21 (Pubitemid 44739952)
16. Moriya, R.; Sano, H.; Umeda, T.; Ito, M.; Takahashi, Y.; Matsuda, M.; Ishihara, A.; Kanatani, A.; Iwaasa, H. RFamide peptide QRFP43 causes obesity with hyperphagia and reduced thermogenesis in mice Endocrinology 2006, 147, 2916-22 (Pubitemid 43764627)
17. Primeaux, S. D.; Blackmon, C.; Barnes, M. J.; Braymer, H. D.; Bray, G. A. Central administration of the RFamide peptides, QRFP-26 and QRFP-43, increases high fat food intake in rats Peptides 2008, 29, 1994-2000
18. Navarro, V. M.; Fernandez-Fernandez, R.; Nogueiras, R.; Vigo, E.; Tovar, S.; Chartrel, N.; Le Marec, O.; Leprince, J.; Aguilar, E.; Pinilla, L.; Dieguez, C.; Vaudry, H.; Tena-Sempere, M. Novel role of 26RFa, a hypothalamic RFamide orexigenic peptide, as putative regulator of the gonadotropic axis J. Physiol. 2006, 573, 237-49 (Pubitemid 43670871)
19. Patel, S. R.; Murphy, K. G.; Thompson, E. L.; Patterson, M.; Curtis, A. E.; Ghatei, M. A.; Bloom, S. R. Pyroglutamylated RFamide peptide 43 stimulates the hypothalamic-pituitary-gonadal axis via gonadotropin-releasing hormone in rats Endocrinology 2008, 149, 4747-54
20. Ukena, K.; Vaudry, H.; Leprince, J.; Tsutsui, K. Molecular evolution and functional characterization of the orexigenic peptide 26RFa and its receptor in vertebrates Cell Tissue Res. 2011, 343, 475-81
21. Egido, E. M.; Hernandez, R.; Leprince, J.; Chartrel, N.; Vaudry, H.; Marco, J.; Silvestre, R. A. 26RFa, a novel orexigenic neuropeptide, inhibits insulin secretion in the rat pancreas Peptides 2007, 28, 725-30 (Pubitemid 46349320)
22. Baribault, H.; Danao, J.; Gupte, J.; Yang, L.; Sun, B.; Richards, W.; Tian, H. The G-protein-coupled receptor GPR103 regulates bone formation Mol. Cell. Biol. 2006, 26, 709-17 (Pubitemid 43089780)
23. Zhang, Q.; Qiu, P.; Arreaza, M. G.; Simon, J. S.; Golovko, A.; Laverty, M.; Vassileva, G.; Gustafson, E. L.; Rojas-Triana, A.; Bober, L. A.; Hedrick, J. A.; Monsma, F. J., Jr.; Greene, J. R.; Bayne, M. L.; Murgolo, N. J. P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse Genomics 2007, 90, 629-35 (Pubitemid 350016723)
24. Fang, Q.; Liu, Q.; Li, N.; Jiang, T. N.; Li, Y. L.; Yan, X.; Wang, R. Cardiovascular effects of intravenous administered 26RFa, a novel RFamide peptide ligand for GPR103, in anaesthetised rats Eur. J. Pharmacol. 2009, 621, 61-6
25. Yamamoto, T.; Miyazaki, R.; Yamada, T. Intracerebroventricular administration of 26RFa produces an analgesic effect in the rat formalin test Peptides 2009, 30, 1683-8
26. Yamamoto, T.; Miyazaki, R.; Yamada, T.; Shinozaki, T. Anti-allodynic effects of intrathecally and intracerebroventricularly administered 26RFa, an intrinsic agonist for GRP103, in the rat partial sciatic nerve ligation model Peptides 2011, 32, 1262-9
27. Yamamoto, T.; Wada, T.; Miyazaki, R. Analgesic effects of intrathecally administered 26RFa, an intrinsic agonist for GPR103, on formalin test and carrageenan test in rats Neuroscience 2008, 157, 214-22
28. Le Marec, O.; Neveu, C.; Lefranc, B.; Dubessy, C.; Boutin, J. A.; Do-Rego, J. C.; Costentin, J.; Tonon, M. C.; Tena-Sempere, M.; Vaudry, H.; Leprince, J. Structure-activity relationships of a series of analogues of the RFamide-related peptide 26RFa J. Med. Chem. 2011, 54, 4806-14
29. Thuau, R.; Guilhaudis, L.; Segalas-Milazzo, I.; Chartrel, N.; Oulyadi, H.; Boivin, S.; Fournier, A.; Leprince, J.; Davoust, D.; Vaudry, H. Structural studies on 26RFa, a novel human RFamide-related peptide with orexigenic activity Peptides 2005, 26, 779-89 (Pubitemid 40461659)
30. Tyndall, J. D.; Pfeiffer, B.; Abbenante, G.; Fairlie, D. P. Over one hundred peptide-activated G protein-coupled receptors recognize ligands with turn structure Chem. Rev. 2005, 105, 793-826 (Pubitemid 40527376)
31. Kessler, H. Conformation and biological activity of cyclic peptides Angew. Chem., Int. Ed. Engl. 1982, 21, 512-23
32. Che, Y.; Marshall, G. R. Engineering cyclic tetrapeptides containing chimeric amino acids as preferred reverse-turn scaffolds J. Med. Chem. 2006, 49, 111-24 (Pubitemid 43077326)
33. Spatola, A. F. Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins; Marcel Dekker: New York, 1983; Vol. 7, pp 267-357.
34. Cheguillaume, A.; Salaun, A.; Sinbandhit, S.; Potel, M.; Gall, P.; Baudy-Floch, M.; Le Grel, P. Solution synthesis and characterization of aza-beta(3)-peptides (N(alpha)-substituted hydrazino acetic acid oligomers J. Org. Chem. 2001, 66, 4923-9 (Pubitemid 32861814)
35. Dali, H.; Busnel, O.; Hoebeke, J.; Bi, L.; Decker, P.; Briand, J. P.; Baudy-Floc'h, M.; Muller, S. Heteroclitic properties of mixed alpha- and aza-beta3-peptides mimicking a supradominant CD4 T cell epitope presented by nucleosome Mol. Immunol. 2007, 44, 3024-36 (Pubitemid 46412481)
36. Laurencin, M.; Legrand, B.; Duval, E.; Henry, J.; Baudy-Floc'h, M.; Zatylny-Gaudin, C.; Bondon, A. From a marine neuropeptide to antimicrobial pseudopeptides containing aza-β(3)-amino acids: structure and activity J. Med. Chem. 2012, 55, 2025-34
37. Perczel, A.; Fasman, G. D. Quantitative analysis of cyclic beta-turn models Protein Sci. 1992, 1, 378-95 (Pubitemid 23007305)
38. Perczel, A.; Hollosi, M.; Tusnady, G.; Fasman, G. D. Convex constraint analysis: a natural deconvolution of circular dichroism curves of proteins Protein Eng. 1991, 4, 669-79
39. Reed, J.; Reed, T. A. A set of constructed type spectra for the practical estimation of peptide secondary structure from circular dichroism Anal. Biochem. 1997, 254, 36-40 (Pubitemid 27523226)
40. Rozek, A.; Friedrich, C. L.; Hancock, R. E. Structure of the bovine antimicrobial peptide indolicidin bound to dodecylphosphocholine and sodium dodecyl sulfate micelles Biochemistry 2000, 39, 15765-74 (Pubitemid 32040945)
41. Rose, G. D.; Gierasch, L. M.; Smith, J. A. Turns in peptides and proteins Adv. Protein Chem. 1985, 37, 1-109
42. Crisma, M.; Fasman, G. D.; Balaram, H.; Balaram, P. Peptide models for beta-turns. A circular dichroism study Int. J. Pept. Protein Res. 1984, 23, 411-9
43. Schmidt, B.; Lindman, S.; Tong, W.; Lindeberg, G.; Gogoll, A.; Lai, Z.; Thornwall, M.; Synnergren, B.; Nilsson, A.; Welch, C. J.; Sohtell, M.; Westerlund, C.; Nyberg, F.; Karlen, A.; Hallberg, A. Design, synthesis, and biological activities of four angiotensin II receptor ligands with gamma-turn mimetics replacing amino acid residues 3-5 J. Med. Chem. 1997, 40, 903-19 (Pubitemid 27131620)
44. Schmidt, J. M.; Ohlenschlager, O.; Ruterjans, H.; Grzonka, Z.; Kojro, E.; Pavo, I.; Fahrenholz, F. Conformation of [8-arginine]vasopressin and V1 antagonists in dimethyl sulfoxide solution derived from two-dimensional NMR spectroscopy and molecular dynamics simulation Eur. J. Biochem. 1991, 201, 355-71
45. Cann, J. R.; London, R. E.; Matwiyoff, N. A.; Stewart, J. M. A combined spectroscopic study of the solution conformation of bradykinin Adv. Exp. Med. Biol. 1983, 156, 495-500
46. Leprince, J.; Oulyadi, H.; Vaudry, D.; Masmoudi, O.; Gandolfo, P.; Patte, C.; Costentin, J.; Fauchere, J. L.; Davoust, D.; Vaudry, H.; Tonon, M. C. Synthesis, conformational analysis and biological activity of cyclic analogs of the octadecaneuropeptide ODN. Design of a potent endozepine antagonist Eur. J. Biochem. 2001, 268, 6045-57 (Pubitemid 33132026)
47. Yuan, Z.; Blomberg, D.; Sethson, I.; Brickmann, K.; Ekholm, K.; Johansson, B.; Nilsson, A.; Kihlberg, J. Synthesis and pharmacological evaluation of an analogue of the peptide hormone oxytocin that contains a mimetic of an inverse gamma-turn J. Med. Chem. 2002, 45, 2512-9 (Pubitemid 34595220)
48. Chatenet, D.; Dubessy, C.; Leprince, J.; Boularan, C.; Carlier, L.; Segalas-Milazzo, I.; Guilhaudis, L.; Oulyadi, H.; Davoust, D.; Scalbert, E.; Pfeiffer, B.; Renard, P.; Tonon, M. C.; Lihrmann, I.; Pacaud, P.; Vaudry, H. Structure-activity relationships and structural conformation of a novel urotensin II-related peptide Peptides 2004, 25, 1819-30 (Pubitemid 39346227)
49. Busnel, O.; Baudy-Floch, M. Preparation of new monomers aza-beta 3-amino acids for solid-phase syntheses of aza-beta 3-peptides Tetrahedron Lett. 2007, 48, 5767-5770 (Pubitemid 47068778)
50. Busnel, O.; Bi, L.; Baudy-Floch, M. Synthesis of Fmoc-protected aza-β3-amino acids via reductive amination of glyoxylic acid Tetrahedron Lett. 2005, 46, 7073-7075 (Pubitemid 41253850)
51. Mazarguil, H.; Gouarderes, C.; Tafani, J. A.; Marcus, D.; Kotani, M.; Mollereau, C.; Roumy, M.; Zajac, J. M. Structure-activity relationships of neuropeptide FF: role of C-terminal regions Peptides 2001, 22, 1471-8 (Pubitemid 32770020)
52. Boyle, R. G.; Downham, R.; Ganguly, T.; Humphries, J.; Smith, J.; Travers, S. Structure-activity studies on prolactin-releasing peptide (PrRP). Analogues of PrRP-(19-31)-peptide J. Pept. Sci. 2005, 11, 161-5 (Pubitemid 40347548)
53. Miskolzie, M.; Kotovych, G. The NMR-derived conformation of neuropeptide AF, an orphan G-protein coupled receptor peptide Biopolymers 2003, 69, 201-15 (Pubitemid 36693244)
54. D'Ursi, A. M.; Albrizio, S.; Di Fenza, A.; Crescenzi, O.; Carotenuto, A.; Picone, D.; Novellino, E.; Rovero, P. Structural studies on Hgr3 orphan receptor ligand prolactin-releasing peptide J. Med. Chem. 2002, 45, 5483-91 (Pubitemid 35424966)
55. Liu, Y.; Zhang, Y.; Li, S.; Huang, W.; Liu, X.; Lu, D.; Meng, Z.; Lin, H. Molecular cloning and functional characterization of the first non-mammalian 26RFa/QRFP orthologue in goldfish, Carassius auratus Mol. Cell. Endocrinol. 2009, 303, 82-90
56. Chen, Y. S.; Chen, C. C.; Horng, J. C. Thermodynamic and kinetic consequences of substituting glycine at different positions in a Pro-Hyp-Gly repeat collagen model peptide Biopolymers 2011, 96, 60-8
57. 2 analogues substituting N-Me-Gly for Gly2 or Gly3 Peptides 2004, 25, 1349-54 (Pubitemid 39180067)
58. Salaun, A.; Potel, M.; Roisnel, T.; Gall, P.; Le Grel, P. Crystal structures of aza-β3-peptides, a new class of foldamers relying on a framework of hydrazinoturns J. Org. Chem. 2005, 70, 6499-502 (Pubitemid 41076537)
59. Bourgault, S.; Vaudry, D.; Botia, B.; Couvineau, A.; Laburthe, M.; Vaudry, H.; Fournier, A. Novel stable PACAP analogs with potent activity towards the PAC1 receptor Peptides 2008, 29, 919-32
60. Leprince, J.; Neveu, C.; Lefranc, B.; Guilhaudis, L.; Segalas-Milazzo, I.; Do Rego, J. C.; Tena-Sempere, M.; Tsutsui, K.; Vaudry, H. 26RFa. In Handbook of Biologically Active Peptides, Kastin, A. J., Ed.; Elsevier: New York, 2012.
61. Chartrel, N.; Alonzeau, J.; Alexandre, D.; Jeandel, L.; Alvear-Perez, R.; Leprince, J.; Boutin, J.; Vaudry, H.; Anouar, Y.; Llorens-Cortes, C. The RFamide neuropeptide 26RFa and its role in the control of neuroendocrine functions Front. Neuroendocrinol. 2011, 32, 387-97
62. Leprince, J.; Cosquer, D.; Bellemere, G.; Chatenet, D.; Tollemer, H.; Jegou, S.; Tonon, M. C.; Vaudry, H. Catabolism of the octadecaneuropeptide ODN by prolyl endopeptidase: identification of an unusual cleavage site Peptides 2006, 27, 1561-9 (Pubitemid 43767018)
63. Haley, T. J.; McCormick, W. G. Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse Br. J. Pharmacol. Chemother. 1957, 12, 12-5
64. Symbols and abbreviations are in accord with recommendations of the IUPAC-IUB Joint Commission on Biochemical Nomenclature (Nomenclature and symbolism for amino acids and peptides. Biochem. J. 1984, 219, 345-373) and with the following: A short guide to abbreviations and their use in peptide science. J. Pept. Sci. 2003, 9, 1-8. All optically active amino acids are of the l configuration unless otherwise noted.