Design and synthesis of conformationally constrained glucagon-like peptide-1 derivatives with increased plasma stability and prolonged in vivo activity

Journal of Medicinal Chemistry

Volumn 51, Issue 9, 2008, Pages 2758-2765

  Miranda, Les P ^a   Winters, Katherine A ^a   Gegg, Colin V ^a   Patel, Ankita ^a   Aral, Jennifer ^a   Long, Jason ^a   Zhang, Jingwen ^a   Diamond, Stephanie ^a   Guido, Mark ^a   Stanislaus, Shanaka ^a   Ma, Mark ^a   Li, Hongyan ^a   Rose, Mark J ^a   Poppe, Leszek ^a   Véniant, Murielle M ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 2 METHYLPROPIONIC ACID; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; GLUCOSE; GLUTAMIC ACID; LACTAM; LYSINE;

AMINO ACID SUBSTITUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DIABETES MELLITUS; DRUG ACTIVITY; DRUG CONFORMATION; DRUG DESIGN; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SCREENING; DRUG SELECTIVITY; DRUG STABILITY; DRUG SYNTHESIS; GLUCOSE BLOOD LEVEL; HUMAN; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIMATE; PROTEIN CONFORMATION; WEIGHT REDUCTION;

AMINO ACID SEQUENCE; ANIMALS; BLOOD GLUCOSE; BODY WEIGHT; CHO CELLS; CRICETINAE; CRICETULUS; DRUG DESIGN; GLUCAGON-LIKE PEPTIDE 1; HUMANS; HYPOGLYCEMIC AGENTS; MACACA FASCICULARIS; MICE; MICE, MUTANT STRAINS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PLASMA; POLYETHYLENE GLYCOLS; PROTEIN CONFORMATION; RADIOLIGAND ASSAY; RECEPTORS, GLUCAGON; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 42949175115     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701522b     Document Type: Article

References (54)

1. Moller, D. Perspective on future peptide and protein-based approaches to therapy of metabolic disease. Am. Pharm. Rev. 2006, 9, 91-95.
2. Kieffer, T. J.; Habener, J. F. The glucagon-like peptides. Endocr. Rev. 1999, 20, 876-913.
3. Gutniak, M.; Orskov, C.; Holst, J. J.; Ahren, B.; Efendic, S. Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. N. Engl. J. Med. 1992, 326, 1316-1322.
4. Orskov, C.; Rabenhoj, L.; Wettergren, A.; Kofod, H.; Holst, J. J. Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes 1994, 43, 535-539.
5. Holst, J. J.; Deacon, C. F. New horizons in diabetes therapy. Immunol., Endocr. Metab. Agents Med. Chem. 2007, 7, 49-55.
6. Vilsboll, T.; Krarup, T.; Madsbad, S.; Holst, J. J. No reactive hypoglycaemia in type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose. Diabetic Med. 2001, 18, 144-149.
7. Gromada, J.; Holst, J. J.; Rorsman, P. Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pfluegers Arch. 1998, 435, 583-594.
8. Dillon, J. S.; Tanizawa, Y.; Wheeler, M. B.; Leng, X. H.; Ligon, B. B.; Rabin, D. U.; Yoo-Warren, H.; Permutt, M. A.; Boyd, A. E., III. Cloning and functional expression of the human glucagon-like peptide-1 (GLP-1) receptor. Endocrinology 1993, 133, 1907-1910.
9. Knudsen, L. B. Glucagon-like peptide-1: the basis of a new class of treatment for type 2 diabetes. J. Med. Chem. 2004, 47, 4128-4134.
10. Sebokova, E.; Christ, A. D.; Boehringer, M.; Mizrahi, J. Dipeptidyl peptidase IV inhibitors: the next generation of new promising therapies for the management of type 2 diabetes. Curr. Top. Med. Chem. 2007, 7, 547-555.
11. 2-terminus in type II diabetic patients and in healthy subjects. Diabetes 1995, 44, 1126-1131.
12. Vilsboll, T.; Agerso, H.; Krarup, T.; Holst, J. J. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J. Clin. Endocrinol. Metab. 2003, 88, 220-224.
13. Deacon, C. F.; Knudsen, L. B.; Madsen, K.; Wiberg, F. C.; Jacobsen, O.; Holst, J. J. Dipeptidyl peptidase IV resistant analogs of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity. Diabetologia 1998, 41, 271-278.
14. Knudsen, L. B.; Nielsen, P. F.; Huusfeldt, P. O.; Johansen, N. L.; Madsen, K.; Pedersen, F. Z.; Thogersen, H.; Wilken, M.; Agerso, H. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J. Med. Chem. 2000, 43, 1664-1669.
15. Kolterman, O. G.; Kim, D. D.; Shen, L.; Ruggles, J. A.; Nielsen, L. L.; Fineman, M. S.; Baron, A. D. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am. J. Health-Syst. Pharm. 2005, 62, 173-181.
16. Knudsen, L. B.; Kiel, D.; Teng, M.; Behrens, C.; Bhumralkar, D.; Kodra, J. T.; Holst, J. J.; Jeppesen, C. B.; Johnson, M. D.; de Jong, J. C.; Jorgensen, A. S.; Kercher, T.; Kostrowicki, J.; Madsen, P.; Olesen, P. H.; Petersen, J. S.; Poulsen, F.; Sidelmann, U. G.; Sturis, J.; Truesdale, L.; May, J.; Lau, J. Small-molecule agonists for the glucagon-like peptide 1 receptor. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 937-942.
17. Adelhorst, K.; Hedegaard, B. B.; Knudsen, L. B.; Kirk, O. Structure-activity studies of glucagon-like peptide-1. J. Biol. Chem. 1994, 269, 6275-6278.
18. Hjorth, S. A.; Adelhorst, K.; Pedersen, B. B.; Kirk, O.; Schwartz, T. W. Glucagon and glucagon-like peptide 1: selective receptor recognition via distinct peptide epitopes. J. Biol. Chem. 1994, 269, 30121-30124.
19. Parker, J. C.; Andrews, K. M.; Rescek, D. M.; Massefski, W., Jr.; Andrews, G. C.; Contillo, L. G.; Stevenson, R. W.; Singleton, D. H.; Suleske, R. T. Structure-function analysis of a series of glucagon-like peptide-1 analogs. J. Pept. Res. 1998, 52, 398-409.
20. Neidigh, J. W.; Fesinmeyer, R. M.; Prickett, K. S.; Andersen, N. H. Exendin-4 and glucagon-like-peptide-1: NMR structural comparisons in the solution and micelle-associated states. Biochemistry 2001, 40, 13188-13200.
21. Chang, X.; Keller, D.; Bjorn, S.; Led, J. J. Structure and folding of glucagon-like peptide-1-(7-36)-amide in aqueous trifluoroethanol studied by NMR spectroscopy. Magn. Reson. Chem. 2001, 39, 477-483.
22. Chang, X.; Keller, D.; O'Donoghue, S. I.; Led, J. J. NMR studies of the aggregation of glucagon-like peptide-1: formation of a symmetric helical dimer. FEBS Lett. 2002, 515, 165-170.
23. Andersen, N. H.; Brodsky, Y.; Neidigh, J. W.; Prickett, K. S. Medium-dependence of the secondary structure of exendin-4 and glucagon-like-peptide-1. Bioorg. Med. Chem. 2002, 10, 79-85.
24. Houston, M. E., Jr.; Gannon, C. L.; Kay, C. M.; Hodges, R. S. Lactam bridge stabilization of a-helical peptides: ring size, orientation and positional effects. J. Pept. Sci. 1995, 1, 274-282.
25. Osapay, G.; Gulyas, J.; Profit, A. A.; Gulyas, E. S.; Taylor, J. W. Multicyclic peptides synthesized using the Kaiser oxime resin: helix stabilizing effects of lactam bridges. Pept.: Chem. Biol., Proc. Am. Pept. Symp., 12th 1992, 239-240.
26. Osapay, G.; Taylor, J. W. Multicyclic polypeptide model compounds. 2. Synthesis and conformational properties of a highly a-helical uncosapeptide constrained by three side-chain to side-chain lactam bridges. J. Am. Chem. Soc. 1992, 114, 6966-6973.
27. Hill, P. S.; Smith, D. D.; Slaninova, J.; Hruby, V. J. Bicyclization of a weak oxytocin agonist produces a highly potent oxytocin antagonist. J. Am. Chem. Soc. 1990, 112, 3110-3113.
28. Al-Obeidi, F.; Castrucci, A. M.; Hadley, M. E.; Hruby, V. J. Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics. J. Med. Chem. 1989, 32, 2555-2561.
29. Trivedi, D.; Lin, Y.; Ahn, J. M.; Siegel, M.; Mollova, N.; Schram, K. H.; Hruby, V. J. Design and synthesis of conformationally constrained glucagon analogues. J. Med. Chem. 2000, 43, 1714-1722.
30. Tudan, C.; Willick, G. E.; Chahal, S.; Arab, L.; Law, P.; Safari, H.; Merzouk, A. C-Terminal cyclization of an SDF-1 small peptide analogue dramatically increases receptor affinity and activation of the CXCR4 receptor. J. Med. Chem. 2002, 45, 2024-2031.
31. Ahn, J.-M.; Gitu, P. M.; Medeiros, M.; Swift, J. R.; Trivedi, D.; Hruby, V. J. A new approach to search for the bioactive conformation of glucagon: positional cyclization scanning. J. Med. Chem. 2001, 44, 3109-3116.
32. Taylor, J. W. The synthesis and study of side-chain lactam-bridged peptides. Biopolymers 2002, 66, 49-75.
33. Wellings, D. A.; Atherton, E. Standard Fmoc protocols. Methods Enzymol. 1997, 289, 44-67.
34. Atherton, E., Sheppard, R. C., Eds. Solid Phase Peptide Synthesis: A Practical Approach; IRL Press: Oxford, U.K., 1989; p 203.
35. Rink, H. Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methyl ester resin. Tetrahedron Lett. 1987, 28, 3787-3790.
36. Aletras, A.; Barlos, K.; Gatos, D.; Koutsogianni, S.; Mamos, P. Preparation of the very acid-sensitive Fmoc-Lys(Mtt)-OH. Application in the synthesis of side-chain to side-chain cyclic peptides and oligolysine cores suitable for the solid-phase assembly of MAPs and TASPs. Int. J. Pept. Protein Res. 1995, 45, 488-496.
37. Yue, C.; Thierry, J.; Potier, P. 2-Phenylisopropyl esters as carboxyl terminus protecting groups in the fast synthesis of peptide fragments. Tetrahedron Lett. 1993, 34, 323-326.
38. Coste, J.; Le-Nguyen, D.; Castro, B. PyBOP: a new peptide coupling reagent devoid of toxic byproduct. Tetrahedron Lett. 1990, 31, 205-208.
39. Montrose-Rafizadeh, C.; Yang, H.; Rodgers, B. D.; Beday, A.; Pritchette, L. A.; Eng, J. High potency antagonists of the pancreatic glucagon-like peptide-1 receptor. J. Biol. Chem. 1997, 272, 21201-21206.
40. Brasier, A. R.; Ron, D. Luciferase reporter gene assay in mammalian cells. Methods Enzymol. 1992, 216, 386-397.
41. Fan, F.; Wood, K. V. Bioluminescent assays for high-throughput screening. Assay Drug Dev. Technol. 2007, 5, 127-136.
42. Takebe, Y. Luciferase assay: a rapid and sensitive method for the quantitation of transcriptional activity. Med. Immunol. 1989, 18, 425-432.
43. Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 1963, 85, 2149-2154.
44. Thieriet, N.; Alsina, J.; Giralt, E.; Guibe, F.; Albericio, F. Use of Alloc-amino acids in solid-phase peptide synthesis. Tandem deprotection-coupling reactions using neutral conditions. Tetrahedron Lett. 1997, 38, 7275-7278.
45. Banerjee, R.; Basu, G.; Chene, P.; Roy, S. Aib-based peptide backbone as scaffolds for helical peptide mimics. J. Pept. Res. 2002, 60, 88-94.
46. Marshall, G. R.; Hodgkin, E. E.; Langs, D. A.; Smith, G. D.; Zabrocki, J.; Leplawy, M. T. Factors governing helical preference of peptides containing multiple a,a-dialkyl amino acids. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 487-491.
47. Harris, J. M.; Chess, R. B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discovery 2003, 2, 214-221.
48. Roberts, M. J.; Bentley, M. D.; Harris, J. M. Chemistry for peptide and protein PEGylation. Adv. Drug Delivery Rev. 2002, 54, 459-476.
49. Berglund, O.; Frankel, B. J.; Hellman, B. Development of the insulin secretory defect in genetically diabetic (db/db) mouse. Acta Endrocrinol. 1978, 87, 543-551.
50. Maiolini, R.; Ferrua, B.; Quaranta, J. F.; Pinoteau, A.; Euller, L.; Ziegler, G.; Massaeyeff, R. A sandwich method of enzyme-immunoassay. II. Quantification of rheumatoid factor. J. Immunol. Methods 1978, 20, 25-34.
51. Lam, S.; See, S. Exenatide: a novel incretin mimetic agent for treating type 2 diabetes mellitus. Cardiol. Rev. 2006, 14, 205-211.
52. Scott, K. A.; Timothy, H.; Moran, T. H. Am. J. Physiol.: Regul., Integr. Comp. Physiol. 2007, 293, 983-987.
53. Wei, Y.; Mojsov, S. Tissue-specific expression of the human receptor for glucagon-like peptide-1: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995, 385, 219-224.
54. Chou, P. Y.; Fasman, G. D. Prediction of protein conformation. Biochemistry 1974, 13, 222-245.