Development of potent glucagon-like peptide-1 agonists with high enzyme stability via introduction of multiple lactam bridges

Journal of Medicinal Chemistry

Volumn 53, Issue 17, 2010, Pages 6412-6420

  Murage, Eunice N ^a   Gao, Guangzu ^b   Bisello, Alessandro ^b   Ahn, Jung Mo ^a  

^a UNIVERSITY OF TEXAS AT DALLAS   (United States)

^b UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIPEPTIDYL PEPTIDASE IV; GLUCAGON LIKE PEPTIDE 1 DERIVATIVE; LACTAM; MEMBRANE METALLOENDOPEPTIDASE;

ALPHA HELIX; AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CIRCULAR DICHROISM; DEPROTECTION REACTION; DRUG CONFORMATION; DRUG DEGRADATION; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; DRUG TARGETING; ENZYME STABILITY; STRUCTURE ACTIVITY RELATION;

CELL LINE; CIRCULAR DICHROISM; DIPEPTIDYL PEPTIDASE 4; GLUCAGON-LIKE PEPTIDE 1; HUMANS; HYPOGLYCEMIC AGENTS; LACTAMS; NEPRILYSIN; PEPTIDES, CYCLIC; PROTEIN STRUCTURE, SECONDARY; RECEPTORS, GLUCAGON; SOLUTIONS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 77956331314     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100602m     Document Type: Article

References (65)

1. Drucker, D. J. Enhancing Incretin Action for the Treatment of Type 2 Diabetes Diabetes Care 2003, 26, 2929-2940
2. Creutzfeldt, W. The Entero-Insular Axis in Type 2 Diabetes: Incretins as Therapeutic Agents Exp. Clin. Endocrinol. Diabetes 2001, 109, S288-S303
3. Hui, H. X.; Zhao, H. N.; Perfetti, R. Structure and Function Studies of Glucagon-like Peptide-1 (GLP-1): The Designing of a Novel Pharmacotogical Agent for the Treatment of Diabetes Diabetes/Metab. Res. Rev. 2005, 21, 313-331
4. Goke, R.; Conlon, J. M. Receptors for Glucagon-like Peptide-1(7-36) Amide on Rat Insulinoma-Derived Cells J. Endocrinol. 1988, 116, 357-362
5. Holst, J. J.; Orskov, C.; Nielsen, O. V.; Schwartz, T. W. Truncated Glucagon-like Peptide-I, an Insulin-Releasing Hormone from the Distal Gut FEBS Lett. 1987, 211, 169-174
6. Kreymann, B.; Williams, G.; Ghatei, M. A.; Bloom, S. R. Glucagon-like Peptide-1 7-36: A Physiological Incretin in Man Lancet 1987, 2, 1300-1304
7. Drucker, D. J.; Philippe, J.; Mojsov, S.; Chick, W. L.; Habener, J. F. Glucagon-like Peptide I Stimulates Insulin Gene Expression and Increases Cyclic AMP Levels in a Rat Islet Cell Line Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 3434-3438
8. Wang, Y. H.; Perfetti, R.; Greig, N. H.; Holloway, H. W.; DeOre, K. A.; MontroseRafizadeh, C.; Elahi, D.; Egan, J. M. Glucagon-like Peptide-1 Can Reverse the Age-Related Decline in Glucose Tolerance in Rats J. Clin. Invest. 1997, 99, 2883-2889
9. Li, Y.; Cao, X.; Li, L. X.; Brubaker, P. L.; Edlund, H.; Drucker, D. J. β-Cell Pdx1 Expression Is Essential for the Glucoregulatory, Proliferative, and Cytoprotective Actions of Glucagon-like Peptide-1 Diabetes 2005, 54, 482-491
10. Farilla, L.; Bulotta, A.; Hirshberg, B.; Calzi, S. L.; Khoury, N.; Noushmehr, H.; Bertolotto, C.; Di Mario, U.; Harlan, D. M.; Perfetti, R. Glucagon-like Peptide-1 Inhibits Cell Apoptosis and Improves Glucose Responsiveness of Freshly Isolated Human Islets Endocrinology 2003, 144, 5149-5158
11. Buteau, J.; El-Assaad, W.; Rhodes, C. J.; Rosenberg, L.; Joly, E.; Prentki, M. Glucagon-like Peptide-1 Prevents β Cell Glucolipotoxicity Diabetologia 2004, 47, 806-815
12. Creutzfeldt, W. O. C.; Orskov, C.; Kleine, N.; Holst, J. J.; Willms, B.; Nauck, M. A. Glucagonostatic Actions and Reduction of Fasting Hyperglycemia by Exogenous Glucagon-like Peptide I(7-36) Amide in Type I Diabetic Patients Diabetes Care 1996, 19, 580-586
13. Turton, M. D.; OShea, D.; Gunn, I.; Beak, S. A.; Edwards, C. M. B.; Meeran, K.; Choi, S. J.; Taylor, G. M.; Heath, M. M.; Lambert, P. D.; Wilding, J. P. H.; Smith, D. M.; Ghatei, M. A.; Herbert, J.; Bloom, S. R. A Role for Glucagon-like Peptide-1 in the Central Regulation of Feeding Nature 1996, 379, 69-72
14. Willms, B.; Werner, J.; Holst, J. J.; Orskov, C.; Creutzfeldt, W.; Nauck, M. A. Gastric Emptying Glucose Responses, and Insulin Secretion after a Liquid Test Meal: Effects of Exogenous Glucagon-like Peptide-1 (GLP-1)-(7-36) Amide in Type 2 (noninsulin-dependent) Diabetic Patients J. Clin. Endocr. Metab. 1996, 81, 327-332
15. Meier, J. J.; Gallwitz, B.; Salmen, S.; Goetze, O.; Holst, J. J.; Schmidt, W. E.; Nauck, M. A. Normalization of Glucose Concentrations and Deceleration of Gastric Emptying after Solid Meals during Intravenous Glucagon-like Peptide-1 in Patients with Type 2 Diabetes J. Clin. Endocr. Metab. 2003, 88, 2719-2725
16. Schjoldager, B. T.; Mortensen, P. E.; Christiansen, J.; Orskov, C.; Holst, J. J. GLP-1 (glucagon-like peptide 1) and Truncated GLP-1, Fragments of Human Proglucagon, Inhibit Gastric Acid Secretion in Humans Dig. Dis. Sci. 1989, 34, 703-708
17. Orskov, C.; Wettergren, A.; Holst, J. J. Biological Effects and Metabolic Rates of Glucagon-like Peptide-1 7-36 Amide and Glucagon-like Peptide-1 7-37 in Healthy Subjects Are Indistinguishable Diabetes 1993, 42, 658-661
18. Deacon, C. F. Therapeutic Strategies Based on Glucagon-like Peptide 1 Diabetes 2004, 53, 2181-2189
19. Mentlein, R.; Gallwitz, B.; Schmidt, W. E. Dipeptidyl peptidase-IV Hydrolyzes Gastric-Inhibitory Polypeptide, Glucagon-Like Peptide-1(7-36)Amide, Peptide Histidine Methionine and Is Responsible for Their Degradation in Human Serum Eur. J. Biochem. 1993, 214, 829-835
20. HupeSodmann, K.; Goke, R.; Goke, B.; Thole, H. H.; Zimmerman, B.; Voigt, K.; McGregor, G. P. Endoproteolysis of Glucagon-like Peptide (GLP)-1(7-36) Amide by Ectopeptidases in RINm5F Cells Peptides 1997, 18, 625-632
21. Mentlein, R. Proline Residues in the Maturation and Degradation of Peptide Hormones and Neuropeptides FEBS Lett. 1988, 234, 251-256
22. Kieffer, T. J.; Mcintosh, C. H. S.; Pederson, R. A. Degradation of Glucose-Dependent Insulinotropic Polypeptide and Truncated Glucagon-Like Peptide-1 in-Vitro and in-Vivo by Dipeptidyl Peptidase-IV Endocrinology 1995, 136, 3585-3596
23. Deacon, C. F.; Johnsen, A. H.; Holst, J. J. Degradation of Glucagon-like Peptide-1 by Human Plasma in-Vitro Yields an N-Terminally Truncated Peptide That Is a Major Endogenous Metabolite in-Vivo J. Clin. Endocr. Metab. 1995, 80, 952-957
24. Kim, D.; Wang, L.; Beconi, M.; Eiermann, G. J.; Fisher, M. H.; He, H.; Hickey, G. J.; Kowalchick, J. E.; Leiting, B.; Lyons, K.; Marsilio, F.; McCann, M. E.; Patel, R. A.; Petrov, A.; Scapin, G.; Patel, S. B.; Roy, R. S.; Wu, J. K.; Wyvratt, M. J.; Zhang, B. B.; Zhu, L.; Thornberry, N. A.; Weber, A. E. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H) -yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A Potent, Orally Active Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes J. Med. Chem. 2005, 48, 141-151
25. Deacon, C. F.; Carr, R. D.; Holst, J. J. DPP-4 Inhibitor Therapy: New Directions in the Treatment of Type 2 Diabetes Front. Biosci. 2008, 13, 1780-1794
26. Lankas, G. R.; Leiting, B.; Roy, R. S.; Eiermann, G. J.; Beconi, M. G.; Biftu, T.; Chan, C. C.; Edmondson, S.; Feeney, W. P.; He, H.; Ippolito, D. E.; Kim, D.; Lyons, K. A.; Ok, H. O.; Patel, R. A.; Petrov, A. N.; Pryor, K. A.; Qian, X.; Reigle, L.; Woods, A.; Wu, J. K.; Zaller, D.; Zhang, X.; Zhu, L.; Weber, A. E.; Thornberry, N. A. Dipeptidyl Peptidase IV Inhibition for the Treatment of Type 2 Diabetes: Potential Importance of Selectivity over Dipeptidyl Peptidases 8 and 9 Diabetes 2005, 54, 2988-2994
27. Kirby, M.; Yu, D. M. T.; O'Connor, S. P.; Gorrell, M. D. Inhibitor Selectivity in the Clinical Application of Dipeptidyl Peptidase-4 Inhibition Clin. Sci. 2010, 118, 31-41
28. Green, B. D.; Flatt, P. R.; Bailey, C. J. Dipeptidyl Peptidase IV (DPP IV) Inhibitors: A Newly Emerging Drug Class for the Treatment of Type 2 Diabetes Diabetes Vasc. Dis. Res. 2006, 3, 159-165
29. Havale, S. H.; Pal, M. Medicinal Chemistry Approaches to the Inhibition of Dipeptidyl Peptidase-4 for the Treatment of Type 2 Diabetes Bioorg. Med. Chem. 2009, 17, 1783-1802
30. Turner, A. J.; Isaac, R. E.; Coates, D. The Neprilysin (NEP) Family of Zinc Metalloendopeptidases: Genomics and Function BioEssays 2001, 23, 261-269
31. Deacon, C. F.; Plamboeck, A.; Holst, J. J.; Carr, R. D. Neutral Endopeptidase 24.11 Inhibition Improves Glucose Tolerance in Anaesthetised Pigs Independently of Effects on Active Glucagon-like Peptide-1 Diabetologia 2004, 47, A282
32. Deacon, C. F.; Holst, J. J. Dipeptidyl Peptidase IV Inhibitors: A Promising New Therapeutic Approach for the Management of Type 2 Diabetes Int. J. Biochem. Cell Biol. 2006, 38, 831-844
33. Fiaux, H.; Kuntz, D. A.; Hoffman, D.; Janzer, R. C.; Gerber-Lemaire, S.; Rose, D. R.; Juillerat-Jeanneret, L. Functionalized Pyrrolidine Inhibitors of Human Type II α-Mannosidases as Anti-Cancer Agents: Optimizing the Fit to the Active Site Bioorg. Med. Chem. 2008, 16, 7337-7346
34. Xiao, Q.; Giguere, J.; Parisien, M.; Jeng, W.; St-Pierre, S. A.; Brubaker, P. L.; Wheeler, M. B. Biological Activities of Glucagon-like Peptide-1 Analogues in Vitro and in Vivo Biochemistry 2001, 40, 2860-2869
35. 2 for Receptor Interaction and cAMP Production Eur. J. Med. Chem. 2004, 39, 473-480
36. Agerso, H.; Vicini, P. Pharmacodynamics of NN2211, a Novel Long Acting GLP-1 Derivative Eur. J. Pharm. Sci. 2003, 19, 141-150
37. Madsbad, S. Exenatide and Liraglutide: Different Approaches To Develop GLP-1 Receptor Agonists (Incretin Mimetics): Preclinical and Clinical Results Best Pract. Res., Clin. Endocrinol. Metab. 2009, 23, 463-477
38. 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
39. Nauck, M. A.; Ratner, R. E.; Kapitza, C.; Berria, R.; Boldrin, M.; Balena, R. Treatment with the Human Once-Weekly Glucagon-like Peptide-1 Analog Taspoglutide in Combination with Metformin Improves Glycemic Control and Lowers Body Weight in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Alone: A Double-Blind Placebo-Controlled Study Diabetes Care 2009, 32, 1237-1243
40. Sebokova, E.; Christ, A. D.; Wang, H. Y.; Sewing, S.; Dong, J. Z.; Taylor, J.; Cawthorne, M. A.; Culler, M. D. Taspoglutide, an Analog of Human Glucagon-Like Peptide-1 with Enhanced Stability and in Vivo Potency Endocrinology 2010, 151, 2474-2482
41. Rosenstock, J.; Yang, F.; Reusch, J.; Stewart, M.; Bush, M.; Grp, A. S. Potential of Albiglutide, a Long-Acting GLP-1 Receptor Agonist, in Type 2 Diabetes. A Randomized Controlled Trial Exploring Weekly, Biweekly, and Monthly Dosing Diabetes Care 2009, 32, 1880-1886
42. Siegel, E. G.; Gallwitz, B.; Scharf, G.; Mentlein, R.; Morys-Wortmann, C.; Folsch, U. R.; Schrezenmeir, J.; Drescher, K.; Schmidt, W. E. Biological Activity of GLP-1 Analogues with N-Terminal Modifications Regul. Pept. 1999, 79, 93-102
43. Green, B. D.; Gault, V. A.; O'Harte, F. P. M.; Flatt, P. R. Structurally Modified Analogues of Glucagon-like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP) as Future Antidiabetic Agents Curr. Pharm. Des. 2004, 10, 3651-3662
44. 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
45. Gallwitz, B.; Witt, M.; Paetzold, G.; Moryswortmann, C.; Zimmermann, B.; Eckart, K.; Folsch, U. R.; Schmidt, W. E. Structure/Activity Characterization of Glucagon-Like Peptide-1 Eur. J. Biochem. 1994, 225, 1151-1156
46. Braun, W.; Wider, G.; Lee, K. H.; Wuthrich, K. Conformation of Glucagon in a Lipid Water Interphase by H-1 Nuclear Magnetic-Resonance J. Mol. Biol. 1983, 169, 921-948
47. Karslake, C.; Piotto, M. E.; Pak, Y. K.; Weiner, H.; Gorenstein, D. G. 2D NMR and Structural Model for a Mitochondrial Signal Peptide Bound to a Micelle Biochemistry 1990, 29, 9872-9878
48. Arora, A.; Abildgaard, F.; Bushweller, J. H.; Tamm, L. K. Structure of Outer Membrane Protein A Transmembrane Domain by NMR Spectroscopy Nat. Struct. Biol. 2001, 8, 334-338
49. 9]Glucagon Amide in the Presence of Perdeuterated Dodecylphosphocholine Micelles Biochemistry 2003, 42, 2825-2835
50. Thornton, K.; Gorenstein, D. G. Structure of Glucagon-like Peptide (7-36) Amide in a Dodecylphosphocholine Micelle As Determined by 2D NMR Biochemistry 1994, 33, 3532-3539
51. 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
52. 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
53. Murage, E. N.; Schroeder, J. C.; Beinborn, M.; Ahn, J.-M. Search for α-Helical Propensity in the Receptor-Bound Conformation of Glucagon-like Peptide-1 Bioorg. Med. Chem. 2008, 16, 10106-10112
54. Fry, D. C.; Madison, V. S.; Greeley, D. N.; Felix, A. M.; Heimer, E. P.; Frohman, L.; Campbell, R. M.; Mowles, T. F.; Toome, V.; Wegrzynski, B. B. Solution Structures of Cyclic and Dicyclic Analogues of Growth Hormone Releasing Factor As Determined by Two-Dimensional NMR and CD Spectroscopies and Constrained Molecular Dynamics Biopolymers 1992, 32, 649-666
55. Taylor, J. W. The Synthesis and Study of Side-Chain Lactam-Bridged Peptides Biopolymers 2002, 66, 49-75
56. Underwood, C. R.; Garibay, P.; Knudsen, L. B.; Hastrup, S.; Peters, G. H.; Rudolph, R.; Reedtz-Runge, S. Crystal Structure of Glucagon-like Peptide-1 in Complex with the Extracellular Domain of the Glucagon-like Peptide-1 Receptor J. Biol. Chem. 2010, 285, 723-730
57. Stevens, C. M.; Watanabe, R. Amino Acid Derivatives. 1. Carboallyloxy Derivatives of α-Amino Acids J. Am. Chem. Soc. 1950, 72, 725-727
58. Dangles, O.; Guibe, F.; Balavoine, G.; Lavielle, S.; Marquet, A. Selective Cleavage of the Allyl and Allyloxcarbonyl Groups through Palladium-Catalyzed Hydrostannolysis with Tributyltin Hydride: Application to the Selective Protection Deprotection of Amino Acid Derivatives and in Peptide Synthesis J. Org. Chem. 1987, 52, 4984-4993
59. Syme, C. A.; Zhang, L.; Bisello, A. Caveolin-1 Regulates Cellular Trafficking and Function of the Glucagon-like Peptide 1 Receptor Mol. Endocrinol. 2006, 20, 3400-3411
60. Salomon, Y.; Londos, C.; Rodbell, M. Highly Sensitive Adenylate Cyclase Assay Anal. Biochem. 1974, 58, 541-548
61. Houston, M. E.; Campbell, A. P.; Lix, B.; Kay, C. M.; Sykes, B. D.; Hodges, R. S. Lactam Bridge Stabilization of α-Helices: The Role of Hydrophobicity in Controlling Dimeric versus Monomeric α-Helices Biochemistry 1996, 35, 10041-10050
62. Plamboeck, A.; Holst, J. J.; Carr, R. D.; Deacon, C. F. Neutral Endopeptidase 24.11 and Dipeptidyl Peptidase IV Are Both Mediators of the Degradation of Glucagon-like Peptide 1 in the Anaesthetised Pig Diabetologia 2005, 48, 1882-1890
63. Kaiser, E.; Colescot, R. I.; Bossinge, C. D.; Cook, P. I. Color Test for Detection of Free Terminal Amino Groups in Solid-Phase Synthesis of Peptides Anal. Biochem. 1970, 34, 595-598
64. Hancock, W. S.; Battersby, J. E. New Micro-Test for Detection of Incomplete Coupling Reactions in Solid-Phase Peptide-Synthesis Using 2,4,6-Trinitrobenzene-Sulphonic Acid Anal. Biochem. 1976, 71, 260-264
65. Ueda, T.; Tomita, K.; Notsu, Y.; Ito, T.; Fumoto, M.; Takakura, T.; Nagatome, H.; Takimoto, A.; Mihara, S.; Togame, H.; Kawamoto, K.; Iwasaki, T.; Asakura, K.; Oshima, T.; Hanasaki, K.; Nishimura, S.; Kondo, H. Chemoenzymatic Synthesis of Glycosylated Glucagon-like Peptide 1: Effect of Glycosylation on Proteolytic Resistance and in Vivo Blood Glucose-Lowering Activity J. Am. Chem. Soc. 2009, 131, 6237-6245