Rationally designed cyclic analogues of luteinizing hormone-releasing hormone: Enhanced enzymatic stability and biological properties

European Journal of Medicinal Chemistry

Volumn 58, Issue , 2012, Pages 237-247

  Laimou, Despina ^a   Katsila, Theodora ^b   Matsoukas, John ^a   Schally, Andrew ^d,e   Gkountelias, Kostas ^c   Liapakis, George ^c   Tamvakopoulos, Constantin ^b   Tselios, Theodore ^a  

^a UNIVERSITY OF PATRAS   (Greece)

^b BIOMEDICAL RESEARCH FOUNDATION   (Greece)

^c UNIVERSITY OF CRETE   (Greece)

^d UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF MIAMI   (United States)

Author keywords

Amide linked cyclization; Cyclic peptide analogues; Hormone dependent cancer; Luteinizing hormone releasing hormone; Medicinal chemistry

Indexed keywords

AMIDE; CETRORELIX; LEUCINE; LEUPRORELIN; PROLINE;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; BIOLOGICAL ACTIVITY; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; CYCLIZATION; DOSE RESPONSE; DRUG DESIGN; DRUG EFFICACY; DRUG RECEPTOR BINDING; DRUG STABILITY; DRUG SYNTHESIS; EMBRYO; ENZYME STABILITY; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; TESTOSTERONE RELEASE;

AMIDES; ANIMALS; CELLS, CULTURED; DRUG DESIGN; GONADOTROPIN-RELEASING HORMONE; HEK293 CELLS; HUMANS; MALE; MICE; MICE, INBRED C57BL; MOLECULAR STRUCTURE; PROTEIN STABILITY; RECEPTORS, LHRH;

EID: 84868261962     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2012.09.043     Document Type: Article

References (56)

1. A.V. Schally, A. Arimura, A.J. Kastin, H. Matsuo, Y. Baba, T.W. Redding, R.M. Nair, L. Debeljuk, and W.F. White Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones Science 173 1971 1036 1038
2. P.M. Conn, and W.F. Crowley Gonadotropin-releasing hormone and its analogues N. Engl. J. Med. 324 1991 93 103
3. E. Hazum, and P.M. Conn Molecular mechanism of gonadotropin releasing hormone (GnRH) action. I. The GnRH receptor Endocrinol. Rev. 9 1988 379 386
4. A.V. Schally, T.W. Redding, and A.M. Comaru-Schally Potential use of analogues of luteinizing hormone-releasing hormones in the treatment of hormone-sensitive neoplasms Cancer Treat. Rep. 68 1984 281 289
5. A.V. Schally LH-RH analogues: I. Their impact on reproductive medicine Gynecol. Endocrinol. 13 1999 401 409
6. A.V. Schally Luteinizing hormone releasing-hormone analogues: their impact on the control of tumorigenesis Peptides 20 1999 1247 1262
7. K.L. Anderes, D.R. Luthin, R. Castillo, E.A. Kraynov, M. Castro, K. Nared Hood, M.L. Gregory, V.P. Pathak, L.C. Christie, G. Paderes, H. Vazir, Q. Ye, M.B. Anderson, and J.M. May Biological characterization of a novel, orally active small molecule gonadotropin-releasing hormone (GnRH) antagonist using castrated and intact rats J. Pharmacol. Exp. Ther. 305 2003 688 695
8. G. Mezo, and M. Manea Receptor-mediated tumor targeting based on peptide hormones Expert Opin. Drug Deliv. 7 2010 79 96
9. M. Marberger, A.V. Kaisary, N.D. Shore, G.S. Karlin, C. Savulsky, R. Mis, C. Leuratti, and J.R. Germa Effectiveness, pharmacokinetics, and safety of a new sustained-release leuprolide acetate 3.75-mg depot formulation for testosterone suppression in patients with prostate cancer: a Phase III, open-label, international multicenter study Clin. Ther. 32 2010 744 757
10. S.L. Stephenson, and A.J. Kenny The metabolism of neuropeptides. Hydrolysis of peptides by the phosphoramidon-insensitive rat kidney enzyme endopeptidase 2 and by rat microvillar membranes Biochem. J. 255 1988 45 51
11. Z. Sofianos, T. Katsila, N. Kostomitsopoulos, V. Balafas, J. Matsoukas, T. Tselios, and C. Tamvakopoulos In vivo evaluation and in vitro metabolism of leuprolide in mice - mass spectrometry-based biomarker measurement for efficacy and toxicity J. Mass Spectrom. 43 2008 1381 1392
12. T. Katsila, E. Balafas, G. Liapakis, P. Limonta, M. Montagnani Marelli, K. Gkountelias, T. Tselios, N. Kostomitsopoulos, J. Matsoukas, and C. Tamvakopoulos Evaluation of a stable gonadotropin releasing hormone analogue in mice for the treatment of endocrine disorders and prostate cancer J. Pharmacol. Exp. Ther. 336 2010 613 623
13. A. Leaños-Miranda, A. Ulloa-Aguirre, L.A. Cervini, J.A. Janovick, J. Rivier, and M. Conn Identification of new gonadotrophin-releasing hormone partial agonists J. Endocrinol. 189 2006 509 517
14. G. Jiang, J. Stalewski, R. Galyean, J. Dykert, C. Schteingart, P. Broqua, A. Aebi, M.L. Aubert, G. Semple, P. Robson, K. Akinsanya, R. Haigh, P. Riviere, J. Trojnar, J.L. Junien, and J. Rivier GnRH antagonists: a new generation of long acting analogues incorporating p-ureido-phenylalanines at positions 5 and 6 J. Med. Chem. 44 2001 453 467
15. M.P. Samant, J. Gulyas, D.J. Hong, G. Croston, C. Rivier, and J. Rivier Synthesis, in vivo and in vitro biological activity of novel azaline B analogues J. Chem. Lett. 15 2005 2894 2897
16. M.P. Samant, R. White, D.J. Hong, G. Croston, P.M. Conn, J.A. Janovick, and J. Rivier Structure-activity relationship studies of gonadotropin-releasing hormone antagonists containing S-aryl/alkyl norcysteines and their oxidized derivatives J. Med. Chem. 50 2007 2067 2077
17. J.E. Rivier, J. Porter, L.A. Cervini, S.L. Lahrichi, D.A. Kirby, R.S. Struthers, S.C. Koerber, and C.L. Rivier Design of monocyclic (1-3) and dicyclic (1-3/4-10) gonadotropin releasing hormone (GnRH) antagonists J. Med. Chem. 43 2000 797 806
18. J.E. Rivier, R.S. Struthers, J. Porter, S.L. Lahrichi, G. Jiang, L.A. Cervini, M. Ibea, D.A. Kirby, S.C. Koerber, and C.L. Rivier Design of potent dicyclic (4-10/5-8) gonadotropin releasing hormone (GnRH) antagonists J. Med. Chem. 43 2000 784 796
19. M.P. Samant, J. Gulyas, D.J. Hong, G. Croston, C. Rivier, and J. Rivier Iterative approach to the discovery of novel degarelix analogues: substitutions at positions 3, 7, and 8 Part II J. Med. Chem. 48 2005 4851 4860
20. M.P. Samant, D.J. Hong, G. Croston, C. Rivier, and J. Rivier Novel analogues of degarelix incorporating hydroxy-, methoxy-, and pegylated-urea moieties at positions 3, 5, 6 and the N-terminus Part III J. Med. Chem. 49 2006 3536 3543
21. J. Matsoukas, J. Hondrelis, G. Agelis, K. Barlos, D. Gatos, R. Ganter, D. Moore, and G. Moore Novel synthesis of cyclic amide-linked analogues of angiotensins II and III J. Med. Chem. 37 1994 2958 2969
22. P. Roumelioti, T. Tselios, K. Alexopoulos, T. Mavromoustakos, A. Kolocouris, G. Moore, and J. Matsoukas Structural comparison between type I and type II antagonists: possible implications in the drug design of AT1 antagonists Bioorg. Med. Chem. Lett. 10 2000 755 758
23. T. Tselios, I. Daliani, L. Probert, S. Deraos, E. Matsoukas, S. Roy, J. Pires, G. Moore, and J. Matsoukas Treatment of experimental allergic encephalomyelitis (EAE) induced by guinea pig myelin basic protein epitope 72-85 with a human MBP(87-99) analogue and effects of cyclic peptides Bioorg. Med. Chem. 8 2000 1903 1909
24. T. Tselios, I. Daliani, S. Deraos, S. Thymianou, E. Matsoukas, A. Troganis, I. Gerothanassis, A. Mouzaki, T. Mavromoustakos, L. Probert, and J. Matsoukas Treatment of experimental allergic encephalomyelitis (EAE) by a rationally designed cyclic analogue of myelin basic protein (MBP) epitope 72-85 Bioorg. Med. Chem. Lett. 18 2000 2713 2717
25. T. Tselios, V. Apostolopoulos, I. Daliani, S. Deraos, S. Grdadolnik, T. Mavromoustakos, M. Melachrinou, S. Thymianou, L. Probert, A. Mouzaki, and J. Matsoukas Antagonistic effects of human cyclic MBP(87-99) altered peptide ligands in experimental allergic encephalomyelitis and human T-cell proliferation J. Med. Chem. 45 2002 275 283
26. J. Matsoukas, V. Apostolopoulos, H. Kalbacher, A.M. Papini, T. Tselios, K. Chatzantoni, T. Biagioli, F. Lolli, S. Deraos, P. Papathanassopoulos, A. Troganis, E. Mantzourani, T. Mavromoustakos, and A. Mouzaki The design and synthesis of a novel potent myelin basic protein epitope 87-99 cyclic analogue: enhanced stability and biological properties of mimics render them a potentially new class of immunomodulators J. Med. Chem. 10 2005 1470 1480
27. Z. Spyranti, G.A. Dalkas, G.A. Spyroulias, E.D. Mantzourani, T. Mavromoustakos, I. Friligou, J.M. Matsoukas, and T.V. Tselios Putative bioactive conformations of amide linked cyclic myelin basic protein peptide analogues associated with experimental autoimmune encephalomyelitis J. Med. Chem. 50 2007 6039 6047
28. E.D. Mantzourani, K. Blokar, T.V. Tselios, J.M. Matsoukas, J.A. Platts, T.M. Mavromoustakos, and S.G. Grdadolnik A combined NMR and molecular dynamics simulation study to determine the conformational properties of agonists and antagonists against experimental autoimmune encephalomyelitis Bioorg. Med. Chem. 16 2008 2171 2182
29. E.D. Mantzourani, J.A. Platts, A. Brancale, T.M. Mavromoustakos, and T.V. Tselios Molecular dynamics at the receptor level of immunodominant myelin basic protein epitope 87-99 implicated in multiple sclerosis and its antagonists altered peptide ligands: triggering of immune response J. Mol. Graph. Model. 26 2007 471 481
30. E.D. Mantzourani, T.V. Tselios, S. Golič Grdadolnik, J.A. Platts, A. Brancale, G. Deraos, J.M. Matsoukas, and T.M. Mavromoustakos Comparison of proposed putative active conformations of linear altered peptide ligands of myelin basic protein epitope 87-99 by spectroscopic and modelling studies: the role of position 91 and 96 in T-cell receptor activation J. Med. Chem. 49 2006 6683 6691
31. E. Mantzourani, T. Tselios, S.G. Grdadolnik, A. Brancale, J. Matsoukas, and T. Mavromoustakos A putative bioactive conformation for the altered peptide ligand of myelin basic protein and inhibitor of experimental autoimmune encephalomyelitis [Arg91, Ala96]MBP87-99 J. Mol. Graph. Model. 25 2006 17 29
32. M. Katsara, G. Deraos, T. Tselios, J. Matsoukas, and V. Apostolopoulos Design of novel cyclic altered peptide ligands of myelin basic protein MBP83-99 that modulate immune responses in SJL/J mice J. Med. Chem. 51 2008 3971 3978
33. G. Deraos, K. Chatzantoni, M.T. Matsoukas, T. Tselios, S. Deraos, M. Katsara, P. Papathanasopoulos, D. Vynios, V. Apostolopoulos, A. Mouzaki, and J. Matsoukas Citrullination of linear and cyclic altered peptide ligands from myelin basic protein MBP(87-99) epitope elicits a Th1 polarized response by T cells isolated from multiple sclerosis patients: implications in triggering disease J. Med. Chem. 51 2008 7834 7842
34. J. Matsoukas, D. Panagiotopoulos, M. Keramida, T. Mavromoustakos, R. Yamdagni, W. Qiao, G. Moore, M. Saifeddine, and M. Hollenberg Synthesis and contractile activities of cyclic thrombin receptor derived peptide analogues with a Phe-Leu-Leu-Arg motif: importance of the Phe/Arg relative conformation and the primary amino group for activity J. Med. Chem. 39 1996 3585 3591
35. G. Aggelis, A. Resvani, M.T. Matsoukas, T. Tselios, K. Kelaidonis, D. Kalavrizioti, D. Vlahakos, and J. Matsoukas Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: rational design, synthesis and biological evaluation Amino Acids 40 2011 411 420
36. G. Agelis, P. Roumelioti, A. Resvani, S. Durdagi, M.-E. Androutsou, k. Kelaidonis, D. Vlahakos, T. Mavromoustakos, and J. Matsoukas An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies J. Comput. Aided Mol. Des. 24 2010 749 758
37. K. Alexopoulos, P. Fatseas, E. Melissari, D. Vlahakos, P. Roumelioti, T. Mavromoustakos, S. Mihailescu, M.C. Paredes-Carbajal, D. Mascher, and J. Matsoukas Design and synthesis of novel biologically active thrombin receptor non-peptide mimetics based on the pharmacophoric cluster Phe/Arg/NH2 of the Ser42-Phe-Leu-Leu-Arg46 motif sequence: platelet aggregation and relaxant activities J. Med. Chem. 47 2004 3338 3352
38. 9] GnRH: stimulation of gonadotropin gene expression J. Med. Chem. 49 2006 105 110
39. J. Matsoukas, M. Keramida, D. Panagiotopoulos, T. Mavromoustakos, H.L.S. Maia, G. Bigam, D. Pati, H.R. Habibi, and G.J. Moore Structure elucidation and conformational analysis of gonadotropin releasing hormone and its novel synthetic analogue [Tyr(OMe)5, d-Lys6, Aze9NHEt]GnRH: the importance of aromatic clustering in the receptor binding activity Eur. J. Med. Chem. 32 1997 927 940
40. A.V. Schally, J.B. Engel, G. Emons, N.L. Block, and J. Pinski Use of analogues of peptide hormones conjugated to cytotoxic radicals for chemotherapy targeted to receptors on tumors Curr. Drug Deliv. 8 2011 11 25
41. F.A. Momany Conformational analysis of the molecule luteinizing hormone-releasing hormone. 3. Analogue inhibitors and antagonists J. Med. Chem. 21 1978 63 68
42. F.A. Momany Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. 2. Tetrapeptide and decapeptide analogues J. Am. Chem. Soc. 98 1976 2990 3000
43. J.A. Söderhäll, E.E. Polymeropoulos, K. Pqulini, E. Gunther, and R. Kuhne Antagonist and agonist binding models of the human gonadotropin-releasing hormone receptor Biochem. Biophys. Res. Commun. 333 2005 568 582
44. D.K. Laimou, M. Katsara, M.T. Matsoukas, V. Apostolopoulos, A.N. Troganis, and T.V. Tselios Structural elucidation of leuprolide and its analogues in solution: insight into their bioactive conformation Amino Acids 39 2010 1147 1160
45. E. Mantzourani, D. Laimou, M.T. Matsoukas, and T. Tselios Peptides as therapeutic agents or drug leads for autoimmune, hormone dependent and cardiovascular diseases Anti-inflam. & Anti-aller. Agents Med. Chem. 7 2010 294 306
46. T. Tselios, L. Probert, I. Daliani, E. Matsoukas, A. Troganis, I. Gerothanassis, T. Mavromoustakos, G. Moore, and J. Matsoukas Design and synthesis of a potent cyclic analogue of the myelin basic protein epitope MBP72-85: importance of the Ala81 carboxyl group and of a cyclic conformation for induction of experimental allergic encephalomyelitis J. Med. Chem. 42 1999 1170 1177
47. K. Barlos, D. Gatos, J. Hondrelis, J. Matsoukas, G. Moore, W. Schafer, and P. Sotiriou Preparation of new acid-labile resins of sec-alcohol type and their applications in peptide synthesis Liebigs Ann. Chem. 1995 951 955
48. K. Barlos, D. Gatos, and W. Schafer Synthesis of prothymosin R-(ProTR)-R protein consisting of 109 amino acid residues Angew. Chem. Int. Ed. Engl. 30 1991 590 593
49. V. Claassen Intraperitoneal drug administration Neglected Factors in Pharmacology and Neuroscience Research 1994 Elsevier Inc. Amsterdam 46 58
50. R.P. Millar, Z.L. Lu, A.J. Pawson, C.A. Flanagan, K. Morgan, and S.R. Maudsley Gonadotropin-releasing hormone receptors Endocrinol. Rev. 25 2004 235 275
51. K. Morgan, A.J. Stewart, N. Miller, P. Mullen, M. Muir, M. Dodds, F. Medda, D. Harrison, S. Langdon, and R.P. Millar Gonadotropin-releasing hormone receptor levels and cell context affect tumor cell responses to agonist in vitro and in vivo Cancer Res. 68 2008 6331 6340
52. C. Tamvakopoulos Mass spectrometry for the quantification of bioactive peptides in biological fluids Mass Spectrom. Rev. 26 2007 389 402
53. 3-42 in mouse plasma by LC/ESI-MS/MS: preclinical evaluation of DP-IV inhibitors J. Proteome Res. 8 2009 3487 3496
54. T. Kenakin A Pharmacology Primer: Theory, Applications, and Methods third ed. 2009 Elsevier Academic Press
55. G. Liapakis, D. Fitzpatrick, C. Hoeger, J. Rivier, R. Vandlen, and T. Reisine Identification of ligand binding determinants in the somatostatin receptor subtypes 1 and 2 J. Biol. Chem. 271 1996 20331 20339
56. G. Liapakis, C. Hoeger, J. Rivier, and T. Reisine Development of a selective agonist at the somatostatin receptor subtype sstr1 J. Pharmacol. Exp. Ther. 276 1996 1089 1094