Design and synthesis of conformationally constrained glucagon analogues

Journal of Medicinal Chemistry

Volumn 43, Issue 9, 2000, Pages 1714-1722

  Trivedi, Dev ^a   Lin, Ying ^a   Ahn, Jung Mo ^a   Siegel, Mara ^a   Mollova, Nevena N ^b   Schram, Karl H ^b   Hruby, Victor J ^a  

^a University of Arizona   (United States)

^b UNIVERSITY OF ARIZONA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE CYCLASE; GLUCACON[9 ASPARTATE 12 LYSINE 17 LYSINE 18 LYSINE 21 GLUTAMATE]; GLUCAGON; GLUCAGON DERIVATIVE; GLUCAGON RECEPTOR; GLUCAGON[12 LYSINE 15 ASPARTATE]; GLUCAGON[12 LYSINE 21 ASPARTATE]; GLUCAGON[15 ASPARTATE 18 LYSINE]; GLUCAGON[17 LYSINE 18 LYSINE 21 GLUTAMATE]; GLUCAGON[9 ASPARTATE 12 LYSINE]; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CHEMICAL REACTION; CONTROLLED STUDY; DRUG CONFORMATION; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; ENZYME ACTIVITY; MALE; NONHUMAN; RAT; SECOND MESSENGER; STRUCTURE ACTIVITY RELATION;

AMINO ACID SEQUENCE; ANIMALS; CELL MEMBRANE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, THIN LAYER; CIRCULAR DICHROISM; DRUG DESIGN; GASTROINTESTINAL AGENTS; GLUCAGON; LIVER; MALE; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; RATS; RATS, SPRAGUE-DAWLEY; SPECTROMETRY, MASS, FAST ATOM BOMBARDMENT;

EID: 0034108526     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990559d     Document Type: Article

References (54)

1. Jelinek, L. J.; Lok, S.; Rosenberg, G. B.; Smith, R. A.; Grant, F. J.; Biggs, S.; Benseh, P. A.; Kuijber, J. L.; Sheppard, P. O.; Sprecher, C. A.; O'Hara, P. J.; Foster, D.; Walker, K. M.; Chen, L. H. J.; McKernan, P. A.; Kindsvogel, W. Expression Cloning and Signaling Properties of the Rat Glucagon Receptor. Science 1993, 259, 1614-1616.
2. Unger, R. H.; Orci, L. The Essential Role of Glucagon in the Pathogenesis of Diabetes Mellitus. Lancet 1975, 1, 14-16.
3. Tang, E. K. Y.; Houslay, M. D. Glucagon, Vasopressin and Angiotensin All Elicit a Rapid, Transient Increase in Hepatocyte Protein Kinase C Activity. Biochem. J 1992, 283, 341-346.
4. 2+-Mobilizing Hormones in Cultured Hepatocytes. Role of Phosphatidylinositol and Phosphatidylcholine Hydrolysis. Biochem. J. 1991, 257, 371-378.
5. Wakelam, M. J. O.; Murphy, G. J.; Hruby, V. J.; Houslay, M. D. Activation of Two Signal Transduction Systems in Hepatocytes by Glucagon. Nature 1986, 323, 68-71.
6. 2 Identifies Glucagon Antagonists from Weak Partial Agonists/Antagonists. Endocrinology 1996, 137, 3316-3322.
7. Hruby, V. J. Glucagon: Molecular Biology and Structure-Activity. In Molecular and Cellular Endocrinology; Bittar, E. E., Ed.; JAI Press: Greenwich, CT, 1997; 10B, pp 387-401.
8. Hruby, V. J. Structure-Conformation-Activity Studies of Glucagon and Semi-Synthetic Glucagon Analogues. Mol. Cell. Biochem. 1982, 44, 49-64.
9. Hruby, V. J.; Krstenansky, J. L.; McKee, R. L.; Pelton, J. T. Glucagon Structure-Function Relationships. The Use of Glucagon Analogues in Studies of Glucagon Receptor Interactions. Hormonal Control of Gluconeogenesis. In Signal Transmission; Kraus-Friedmann, N., Ed.; CRC Press: Boca Raton, FL, 1986; pp 3-20.
10. Unson, C. G.; MacDonald, D.; Ray, K.; Durrah, T. L.; Merrifield, R. B. Position 9 Replacement Analogues of Glucagon Uncouple Biological Activity and Receptor Binding. J. Biol. Chem. 1991, 266, 2763-2766.
11. Unson, C. G.; Wu, C.-R.; Merrifield, R. B. Roles of Aspartic Acid 15 and 21 in Glucagon Action: Receptor Anchor and Surrogates for Aspartic Acid 9. Biochemistry 1994, 33, 6884-6887.
12. Unson, C. G.; Merrifield, R. B. Identification of an Essential Serine Residue in Glucagon: Implication for an Active Site Triad. Proc. Natl. Acad. Sci. U.S.A. 1994, 97, 454-458.
13. Unson, C. G.; Wu, C.-R.; Cheung, C. P.; Merrifield, R. B. Positively Charged Residues at Positions 12, 17, and 18 of Glucagon Ensure Maximum Biological Potency. J. Biol. Chem. 1998, 273, 10308-10312.
14. Azizeh, B. Y.; Ahn, J.-M.; Caspari, R.; Shenderovich, M.;Trivedi, D.; Hruby, V. J. The Role of Phenylalanine at Position 6 in Glucagon's Mechanism of Biological Action: Multiple Replacement Analogues of Glucagon. J. Med. Chem. 1997, 40, 2555-2562.
15. Azizeh, B. Y.; Shenderovich, M. D.; Trivedi, D.; Li, G.; Sturm, N. S.; Hruby, V. J. Topographical Amino Acid Substitution in Position 10 of Glucagon Leads to Antagonists/Partial Agonists with Greater Binding Differences. J. Med. Chem. 1996, 39, 2449-2455.
16. Krstenansky, J. L.; Trivedi, D.; Hruby, V. J. Importance of the 10-13 Region of Glucagon for Its Receptor Interactions and Activation of Adenylate Cyclase. Biochemistry 1986, 25, 3833-3839.
17. Sturm, N. S.; Lin, Y.; Burley, S. K.; Krstenansky, J. K.; Ahn, J.-M.; Azizeh, B. Y.; Trivedi, D.; Hruby, V. J. Structure-Function Studies on Positions 17, 18 and 21 Replacement Analogues of Glucagon: The Importance of Charged Residues and Salt Bridges in Glucagon Biological Activity. J. Med. Chem. 1998, 41, 2693-2700.
18. Hruby, V. J. Conformational Restrictions of Biologically Active Peptides Via Amino Acid Side Chain Groups. Life Sci. 1972, 31, 189-199.
19. Hruby, V. J.; Al-Obeidi, F.; Kazmierski, W. Emerging Approaches in the Molecular Design of Receptor Selective Peptide Ligands: Conformational, Topographical and Dynamic Considerations. Biochem. J. 1990, 268, 249-262.
20. Sasaki, K.; Dockerill, S.; Adamiak, D. A.; Tickle, I. J.; Blundell, T. X-ray Analysis of Glucagon and Its Relationship to Receptor Binding. Nature (London) 1975, 257, 751-757.
21. Chou, P. Y.; Fasman, G. D. Emperical Predictions of Protein Conformation. Annu. Rev. Bioehem. 1978, 47, 251-276.
22. Schiffer, M.; Edmundson, A. B. Use of Helical Wheels to Represent the Structures of Proteins and to Identify Segments with Helical Potential. Biophys. J. 1967, 7, 121-135.
23. Schiffer, M.; Edmundson, A. B. Correlation of Amino Acid Sequence and Conformation in Tabacco Mosaic Virus. Biophys. J. 1968, 8, 29-39.
24. Kuntz, I. D. Protein Folding. J. Am. Chem. Soc. 1972, 94, 4009-4012.
25. Korn, A. P.; Ottensmeyer, F. P. A Model for the Three-Dimensional Structure of Glucagon. J. Theor. Biol. 1983, 105, 403-425.
26. Hruby, V. J.; Krstenansky, J. L.; Gysin, B.; Pelton, J. T.; Trivedi, D.; McKee, R. L. Conformational Considerations in the Design of Glucagon Agonists and Antagonists: Examination Using Synthetic Analogues. Biopolymers 1986, 25, 135-155.
27. 1H Nuclear Magnetic Resonance. J. Mol. Biol. 1983, 169, 921-948.
28. Srere, P. A.; Brooks, G. The Circular Dichroism of Glucagon in Solution. Arch. Biochem. Biophys. 1969, 129, 708-710.
29. Krstenansky, J. L.; Zechel, C.; Trivedi, D.; Hruby, V. J. Importance of the C-Terminal α-Helical Structure for Glucagon's Biological Activity. Int. J. Pept. Protein Res. 1988, 32, 468-478.
30. Hruby, V. J.; Al-Obeidi, F.; Sanderson, D. G.; Smith. D. D. Synthesis of Cyclic Peptides by Solid-Phase Methods. In Innovations and Perspectives in Solid-Phase Synthesis; Epton, R., Ed.; SPCC (UK) Ltd.: Birmingham, 1990; pp 197-203.
31. 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, 772, 3110-3113.
32. Lebl, M.; Hill, P.; Kazmierski, W.; Karasova, L.; Slaninova, J.; Fric, L; Hruby, V. J. Conformationally Restricted Analogues of Oxytocin Stabilization of Inhibitory Conformation. Int. J. Pept. Protein Res. 1990, 36, 321-330.
33. Smith, D. D.; Slaninova, J.; Hruby, V. J. Structure-Activity Studies of a Novel Bicyclic Oxytocin Antagonist. J. Med. Chem. 1992, 35, 1558-1563.
34. Al-Obeidi, F.; Hadley. M. E.; Pettitt, B. M.; Hruby, V. J. Design of a New Class of Superpotent Cyclic α-Melanotropins Based on Quenched Dynamic Simulations. J. Am. Chem. Soc. 1989, 777, 3413-3416.
35. Al-Obeidi, F.; Castrucci, A. M. de L.; Hadley, M. E.; Hruby, V. J. Potent and Prolonged Acting Cyclic Lactam Analogues of α-Melanotropin: Design Based on Molecular Dynamics. J. Med. Chem. 1989, 32, 2555-2561.
36. Lin, Y.; Trivedi, D.; Siegel, M.; Hruby, V. J. Conformationally Constrained Glucagon Analogues: New Evidence for the Conformational Features Important to Glucagon-Receptor Interactions. In Peptide: Chemistry and Biology; Smith, J. A.; Rivier, J. E., Eds.; ESCOM: Leiden, The Netherlands, 1992; pp 439-440.
37. N2 Deprotection of Synthetic Peptides with a Low Concentration of HF in Dimethyl Sulfide: Evidence and Application in Peptide Synthesis. J. Am. Chem. Soc. 1983, 105, 6442-6455.
38. Mollova, N. N.; Schram, K. H.; Lin, Y.; Dharanipragada, R.; Hruby, V. J. Characterization of Linear and Cyclic Glucagon Analogues by Fast Atom Bombardment Mass Spectrometry. J. Bio. Mass Spectr. 1993, 22, 267-276.
39. Pohl, S. L.; Birnbaumer, L.; Rodbell, M. The Glucagon Sensitive Adenylate System in Plasma Membranes. J. Biol. Chem. 1971, 246, 1849-1856.
40. Krstenansky, J. L.; Trivedi, D.; Johnson, D.; Hruby, V. J. Conformational Considerations in the Design of a Glucagon Analogue with Increased Receptor Binding and Adenylate Cyclase Potencies. J. Am. Chem. Soc. 1986, 108, 1696-1698.
41. Meraldi, J.-P.; Hruby, V. J.; Brewster, A. I. R. Relative Conformational Rigidity in Oxytocin and [1-Penicillamine]Oxytocin: A Proposal for the Relationship of Conformational Flexibility to Peptide Hormone Agonism and Antagonism. Proc. Natl. Acad. Sci. U.S.A. 1977, 74, 1373-1377.
42. Unson, C. G.; Andreu, D.; Gurzenda, E. M.; Merrifield, R. B. Synthetic Peptide Antagonist of Glucagon. Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 4083-4087.
43. Kaiser, E.; Colescott, R. L.; Bossinger, C. D.; Cook, P. L. Color Test for Detection of Free Terminal Amino Groups in the Solid-Phase Synthesis of Peptides. Anal. Biochem. 1970, 34, 595-598.
44. Neville, D. M. Isolation of an Organ-Specific Protein Antigen from All Surface Membrane of Rat Liver. Biochim. Biophys. Acta. 1968, 154, 540-552.
45. Markwell, M. A. K.; Haas, S. M.; Bieber, L. L.; Tolbert, N. E. A Modification of the Lowry Procedure of Simplifying Protein Determination in Membrane and Lipoprotein Samples, Anal. Biochem. 1978, 87, 206-210.
46. 125I]Monoiodoglucagon by Isolated Canine Hepatocytes. J. Biol. Chem. 1983, 259, 8986-8993.
47. 125I-Glucagon by Anion Exchange Chromatography. Horm. Metab. Res. 1972, 48, 223-224.
48. 22-Glucagon. Biochemistry 1975, 14, 1559-1563.
49. Salomon, Y.; Londos, C.; Rodbell, M. A Highly Sensitive Adenylate Cyclase Assay. Anal. Biochem. 1974, 58, 541-548.
50. Cassim, J. Y.; Yang, J. T. A Computarized Calibration of the Circular Dichrometer. Biochemistry 1969, 8, 1947-1951.
51. Yang, J. T.; Wu, C.-S.; Martinez, H. M. Calculation of Protein Conformation from Circular Dichroism. In Methods in Enzymol-ogy; Hirs, C. H. W., Timasheff, S. N., Eds.; Academic Press: Orlando, FL, 1986; Vol. 130, p 228.
52. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. MacroModel -An Integrated Software System for Modeling Organic and Bioorganic Molecules Using Molecular Mechanics. J. Comput. Chem. 1990, 11, 440-467.
53. Weiner, S. J.; Kollam, P. A.; Case, D. A. All-Atom Force Field for Simulations of Proteins and Nucleic Acids. J. Comput. Chem. 1986, 7, 230-252.
54. Still, W. C.; Tempczyk, A.; Hawley, R. C.; Hendrickson, T. Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. J. Am. Chem. Soc. 1990, 112, 6127-6129.