De Novo Design, Synthesis, and Pharmacology of α-Melanocyte Stimulating Hormone Analogues Derived from Somatostatin by a Hybrid Approach

Journal of Medicinal Chemistry

Volumn 47, Issue 6, 2004, Pages 1514-1526

  Han, Guoxia ^a   Haskell Luevano, Carrie ^c   Kendall, Laura ^a   Bonner, Gregg ^a   Hadley, Mac E ^b   Cone, Roger D ^d   Hruby, Victor J ^a  

^a University of Arizona   (United States)

^b UNIVERSITY OF ARIZONA   (United States)

^c UNIVERSITY OF FLORIDA   (United States)

^d OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERMEDIN; ALPHA INTERMEDIN DERIVATIVE; HALOGEN; LACTAM; LIGAND; MELANOCORTIN RECEPTOR; MU OPIATE RECEPTOR; OCTREOTIDE; SOMATOSTATIN;

ANIMAL CELL; ANIMAL TISSUE; BIOASSAY; CONFERENCE PAPER; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DESIGN; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; FROG; HYBRIDIZATION; MOUSE; NONHUMAN; PEPTIDE SYNTHESIS; PHARMACOPHORE; RAT; SKIN; STEREOCHEMISTRY;

ALPHA-MSH; ANIMALS; CYSTEINE; DRUG DESIGN; MICE; MOLECULAR CONFORMATION; PEPTIDES, CYCLIC; RANA PIPIENS; RATS; RECEPTOR, MELANOCORTIN, TYPE 1; RECEPTOR, MELANOCORTIN, TYPE 3; RECEPTOR, MELANOCORTIN, TYPE 4; RECEPTORS, CORTICOTROPIN; SKIN; SOMATOSTATIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 1542298085     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm030452x     Document Type: Conference Paper

References (94)

1. Hadley, M. E.; Haskell-Luevano, C. The Proopiomelanocortin System. Cutaneous Neuroimmunomodulation: The Proopiomelanocortin System. Ann. N. Y. Acad. Sci. 1999, 885, 1-21.
2. Shizume, K. Thirty-Five Years of Progress in the Study of MSH. Yale J. Biol. Med. 1985, 58, 561-570.
3. Cone, R. D.; Lu, D. S.; Koppula, S.; Vage, D. I.; Klungland, H.; Boston, B.; Chen, W. B.; Orth, D. N.; Pouton, C.; Kesterson, R. A. The Melanocortin Receptors: Agonists, Antagonists, and the Hormonal Control of Igmentation. Recent Prog. Hormone Res. 1996, 51, 287-318.
4. Abdel-Malek, Z.; Suzuki, I.; Tada, A.; Im, S.; Akcali, C. The Melanocortins in Endotoxin-Induced Anorexia. Cutaneous Neuroimmunomodulation: The Proopiomelanocortin System. Ann. N. Y. Acad. Sci. 1999, 885, 117-133.
5. Huang, Q. H.; Hruby, V. J.; Tatro, J. B. Role of Central Melanocortins in Endotoxin-Induced Anorexia. Am. J. Physiol.-Regul. Integr. Comput. Physiol. 1999, 45, R864-R871.
6. Li, S. J.; Varga, K.; Archer, P.; Hruby, V. J.; Sharma, S. D.; Kesterson, R. A.; Cone, R. D.; Kunos, G. Melanocortin Antagonists Define Two Distinct Pathways of Cardiovascular Control by Alpha- and Gamma-Melanocyte-Stimulating Hormones. J. Neurosci. 1996, 16, 5182-5188.
7. Beckwith, B. E.; Tinius, T. P.; Hruby, V. J.; Al-Obeidi, F.; Sawyer, T. K.; Affholter, J. A. The Effects of Structure-Conformation Modifications of Melanotropin Analogues on Learning and Memory: D-Amino-Acid Substituted Linear and Cyclic Analogues. Peptides 1989, 10, 361-368.
8. Huang, Q. H.; Entwistle, M. L.; Alvaro, J. D.; Duman, R. S.; Hruby, V. J.; Tatro, J. B. Antipyretic Role of Endogenous Melanocortins Mediated by Central Melanocortin Receptors During Endotoxin-Induced Fever. J. Neurosci. 1997, 17, 3343-3351.
9. Kunos, G.; Li, S. J.; Varga, K.; Archer, P.; Kesterson, R.A.; Cone, R. D.; Hruby, V. J.; Sharma, S. D. Novel Neural Pathways of Cardiovascular Control by Alpha- and Gamma-MSH. Fundam. Clin. Pharmacol. 1997, 11, S44-S48.
10. Ni, X. P.; Kesterson, R. A.; Sharma, S. D.; Hruby, V. J.; Cone, R. D.; Wiedemann, E.; Humphreys, M. H. Prevention of Reflex Natriuresis After Acute Unilateral Nephrectomy by Melanocortin Receptor Antagonists. Am. J. Physiol.-Regul. Integr. Comput. Physiol. 1998, 43, R931-R938.
11. Argiolas, A.; Melis, M. R. Neuromodulation of Penile Erection: An Overview of the Role of Neurotransmitters and Neuropeptides. Prog. Neurobiol. 1995, 47, 235-255.
12. Scimonelli, T.; Medina, F.; Wilson, C.; Celis, M. E. Interaction of Alpha-Melanotropin (Alpha-MSH) and Noradrenaline in the Median Eminence in the Control of Female Sexual Behavior. Peptides 2000, 21, 219-223.
13. Jaffe, S. B.; Sobieszczyk, S.; Wardlaw, S. L. Effect of Opioid Antagonism on Beta-Endorphin Processing and Proopiomelanocortin-Peptide Release in the Hypothalamus. Brain Res. 1994, 648, 24-31.
14. Kask, A.; Rago, L.; Mutulis, F.; Pahkla, R.; Wikberg, J. E. S.; Schioth, H. B. Selective Antagonist for the Melanocortin 4 Receptor (HS014) Increases Food Intake in Free-Feeding Rats. Biochem. Biophys. Res. Commun. 1998, 245, 90-93.
15. Versteeg, D. H. G.; Van Bergen, P.; Adan, R. A. H.; De Wildt, D. J. Melanocortins and Cardiovascular Regulation. Eur. J. Pharmacol. 1998, 360, 1-14.
16. Hunt, G. Melanocyte-Stimulating Hormone: A Regulator of Human Melanocyte Physiology. Pathobiology 1995, 63, 12-21.
17. Wikberg, J. E. S. Melanocortin Receptors: Perspectives for Novel Drugs. Eur. J. Pharmacol. 1999, 375, 295-310.
18. Cutuli, M.; Cristiani, S.; Lipton, J. M.; Catania, A. Antimicrobial Effects of Alpha-MSH Peptides, J. Leukoc. Biol. 2000, 67, 233-239.
19. Benoit, S. C.; Schwartz, M. W.; Lachey, J. L.; Hagan, M. M.; Rushing, P. A.; Blake, K. A.; Yagaloff, K. A.; Kurylko, G.; Franco, L.; Danho, W.; Seeley, R. J. A Novel Selective Melanocortin-4 Receptor Agonist Reduces Food Intake in Rats and Mice Without Producing Aversive Consequences. J. Neurosci. 2000, 20, 3442-3448.
20. Fan, W.; Boston, B. A.; Kesterson, R. A.; Hruby, V. J.; Cone, R. D. Role of Melanocortinergic Neurons in Feeding and the Agouti Obesity Syndrome. Nature 1997, 385, 165-168.
21. Cone, R. D., Ed. The Melanocortin Receptors; Humana Press: Totowa, New Jersey, 2000; p 551.
22. Wessells, H.; Fuciarelli, K.; Hansen, J.; Hadley, M. E.; Hruby, V. J.; Dorr, R.; Levine, N. Synthetic Melanotropic Peptide Initiates Erections in Men with Psychogenic Erectile Dysfunction: Double-Blind, Placebo Controlled Crossover Study. J. Urol. 1998, 160, 389-393.
23. Strand, F. L. New Vistas for Melanocortins - Finally, An Explanation for their Pleiotropic Functions. Ann. N. Y. Acad. Sci. 1999, 897, 1-16.
24. Tatro, J. B. Receptor Biology of the Melanocortins, A Family of Neuroimmunomodulatory Peptides. Neuroimmunomodulation 1996, 3, 259-284.
25. Hruby, V. J.; Wilkes, B. C.; Cody, W. L.; Sawyer, T. K.; Hadley, M. E. Melanotropoins: Structural, Conformational and Biological Considerations in the Development of Superpotent and Superprolonged Analogues. Pept. Protein Rev. 1984, 3, 1-64.
26. Eberle, A. N. Proopinomelanocortin and the Melanocortin Peptides. In The Melanocortin Receptors; Cone, R. D., Ed.; Humana Press: Totowa, New Jersey, 2000; pp 3-67.
27. Hruby, V. J.; Han, G. The Molecular Pharmacology of "-Melanotropic Stimulating Hormone: Structure-Activity Relationship for Melanotropins at Melanocortin Receptors. In The Melanocortin Receptors; Cone, R. D., Ed.; Humana Press: Totowa, New Jersey, 2000; pp 239-261.
28. Hadley, M. E., Ed., The Melanotropic Peptides: Source, Synthesis, Chemistry, Secretion, Circulation, and Metabolism. CRC Press: Boca Raton, FL, 1988; Vol. I, pp 1-222.
29. Hadley, M. E., Ed., The Melanotropic Peptides: Biological Roles. CRC Press: Boca Raton, FL, 1988; pp 1-198.
30. Hadley, M. E., Ed., The Melanotropic Peptides: Mechanisms of Action and Biomedical Applications. CRC Press: Boca Raton, FL, 1988; pp 1-159.
31. Hruby, V. J.; Sharma, S. D.; Toth, K.; Jaw, J. Y.; Al-Obeidi, F.; Sawyer, T. K.; Hadley, M. E. Design, Synthesis, and Conformation of Superpotent and Prolonged Acting Melanotropins. Ann. N. Y. Acad. Sci. 1993, 680, 51-63.
32. Hadley, M. E.; Hruby, V. J.; Jiang, J.; Sharma, S. D.; Fink, J. L.; Haskell-Luevano, C.; Bentley, D. L.; Al-Obeidi, F.; Sawyer, T. K. Melanocortin Receptors: Identification and Characterization by Melanotropic Peptide Agonists and Antagonists. Pigment Cell Res. 1996, 9, 213-234.
33. Sawyer, T. K.; Sanfilippo, P. J.; Hruby, V. J.; Engel, M. H.; Heward, C. B.; Burnett, J. B.; Hadley, M. E. 4-Norleucine, 7-D-Phenylalanine-Alpha-Melanocyte-Stimulating Hormone: A Highly Potent Alpha-Melanotropin with Ultralong Biological Activity. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 5754-5758.
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, 111, 3413-3416.
35. Al-Obeidi, F.; Castrucci, A. M. D.; 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.
36. Cone, R. D. The Central Melanocortin System and Energy Homeostasis. Trends Endocrinol. Metab. 1999, 10, 211-216.
37. Cone, R. D. The Central Melanocortin System and its Role in Energy Homeostasis. Ann. Endocrinol. 1999, 60, 3-9.
38. 2 with, Bulky Aromatic-Amino-Acids at Position-7 Show High Antagonist Potency and Selectivity at Specific Melanocortin Receptors. J. Med. Chem. 1995, 38, 3454-3461.
39. Schioth, H. B.; Mutulis, F.; MuCeniece, R.; Prusis, P.; Wikberg, J. E. S. Discovery of Novel Melanocortin(4) Receptor Selective MSH Analogues. Br. J. Pharmacol. 1998, 124, 75-82.
40. Haskell-Luevano, C.; Lim, S.; Yuan, W.; Cone, R. D.; Hruby, V. J. Structure Activity Studies of the Melanocortin Antagonist SHU9119 Modified at the 6, 7, 8, and 9 Positions. Peptides 2000, 21, 49-57.
41. Haskell-Luevano, C.; Shenderovich, M. D.; Sharma, S. D.; Nikiforovich, G. V.; Hadley, M. E.; Hruby, V. J. Design, Synthesis, Biology, and Conformations of Bicyclic Alpha-Melanotropin Analogues. J. Med. Chem. 1995, 38, 1736-1750.
42. Bednarek, M. A.; Silva, M. V.; Arison, B.; MacNeil, T.; Kalyani, R. N.; Huang, R. R. C.; Weinberg, D. H. Structure-Function Studies on the Cyclic Peptide MT-II, Lactam Derivative of Alpha-Melanotropin. Peptides 1999, 20, 401-409.
43. Hadley, M. E.; Marwan, M. M.; Al-Obeidi, F.; Hruby, V. J.; Castrucci, A. M. Linear and Cyclic Alpha-Melanotropin [4-10]-Fragment Analogues that Exhibit Superpotency and Residual Activity. Pigment Cell Res. 1989, 2, 478-484.
44. Adan, R. A.; Oosterom, J.; Ludvigsdottir, G.; Brakkee, J. H.; Burbach, J. P.; Gispen, W. H. Identification of Antagonists for Melanocortin MC3, MC4 and MC5 Receptors. Eur. J. Pharmacol. 1994, 269, 331-337.
45. Oosterom, J.; Nijenhuis, W. A. J.; Schaaper, W. M. M.; Slootstra, J.; Meloen, R. H.; Gispen, W. H. H.; Burbach, J. P. H.; Adan, R. A. H. Conformation of the Core Sequence in Melanocortin Peptides Directs Selectivity for the Melanocortin MC3 and MC4 Receptors. J. Biol. Chem. 1999, 274, 16853-16860.
46. Bednarek, M. A.; Macneil, T.; Kalyani, R. N.; Tang, R.; Van der Ploeg, L. H.; Weinberg, D. H. Analogues of MTII, Lactam Derivatives of Alpha-Melanotropin, Modified at the N-Terminus, and their Selectivity at Human Melanocortin Receptors 3, 4, and 5. Biochem. Biophys. Res. Commun. 1999, 261, 209-213.
47. Schioth, H. B.; Muceniece, R.; Mutulis, F.; Bouifrouri, A. A.; Mutule, I.; Wikberg, J. E. S. Further Pharmacological Characterization of the Selective Melanocortin 4 Receptor Antagonist HS014: Comparison with SHU9119. Neuropeptides 1999, 33, 191-196.
48. Bednarek, M. A.; MacNeil, T.; Kalyani, R. N.; Tang, R.; Van der Ploeg, L. H. T.; Weinberg, D. H. Analogues of Lactam Derivatives of Alpha-Melanotropin with Basic and Acidic Residues. Biochem. Biophys. Res. Commun. 2000, 272, 23-28.
49. 8 on Human MC3 Receptor Selectivity. J. Med. Chem. 2000, 43, 4998-5002.
50. Kavarana, M. J.; Trivedi, D.; Cai, M.; Ying, J.; Hammer, M.; Cabello, C. ; Grieco, P.; Han, G.; Hruby, V. J. Novel Cyclic Templates of Alpha-MSH Give Highly Selective and Potent Antagonists/Agonists for Human Melanocortin-3/4 Receptors. J. Med. Chem. 2002, 45, 2644-2650.
51. Grieco, P.; Lavecchia, A.; Cai, M.; Trivedi, D.; Weinberg, D.; MacNeil, T.; Van der Ploeg, L. H. T.; Hruby, V. J. Structure-Activity Studies of the Melanocortin Peptides: Discovery of Potent and Selective Antagonists at MC3 and MC4 Receptors. J. Med. Chem. 2002, 45, 5287-5294.
52. Han, G.; Quillan, J. M.; Carlson, K.; Sadée, W.; Hruby, V. J. Design of Novel Chimeric Melanotropin-Deltorphin Analogues: Discovery of the First Potent Human Melanocortin 1 Receptor Antagonist. J. Med. Chem. 2003, 46, 810-819.
53. Grieco, P.; Han, G.; Weinberg, D.; MacNeil, T.; Van der Ploeg, L. H. T.; Hruby, V. J. Design and Synthesis of Highly Potent and Selective Melanotropin Analogues of SHU9119 Modified at Position 6. Biochem. Biophy. Res. Commun. 2002, 292, 1075-1080.
54. Bednarek, M. A.; MacNeil, T.; Tang, R.; Kalyani, R. N.; Van der Ploeg, L. H. T.; Weinberg, D. H. Potent and Selective Agonist of α-Melanotropin Action at Human Melanocortin Receptor 4. Their Synthesis and Biological Evaluation In Vitro. Biochem. Biophy. Res. Commun. 2001, 686, 641-645.
55. Szardinings, M.; Muceniece, R.; Mutule, I.; Mutulis, F.; Wikberg, J. E. S. New Highly Specific Agonistic Peptides for Human Melanocortin MC1 Receptors. Peptides 2001, 21, 239-243.
56. Wikberg, J. E. S. Melanocortin Receptors: Perspectives for Novel Drugs. Eur. J. Pharmacol. 1999, 375, 295-310.
57. Pelton, J. T.; Gulya, K.; Hruby, V. J.; Duckles, S. P.; Yamamura, H. I. Conformationally Restricted Analogues of Somatostatin with High Mu-Opiate Receptor Specificity. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 236-239.
58. Pelton, J. T.; Gulya, K.; Hruby, V. J.; Duckles, S.; Yamamura, H. I. Somatostatin Analogues with Affinity for Opiate Receptors in Rat-Brain Binding Assay. Peptides 1985, 6, 159-163.
59. Hirning, L. D.; Peterson, L. J.; Pelton, J. T.; Hruby, V. J.; Burks, T. F. Opioid Antagonist Action of Conformationally Constrained Somatostatin Analogues Invitro. Fed. Proc. 1985, 44, 611-611.
60. Pelton, J. T.; Kazmierski, W.; Gulya, K.; Yamamura, H. I.; Hruby, V. J. Design and Synthesis of Conformationally Constrained Somatostatin Analogues with High Potency and Specificity for Mu-Opioid Receptors. J. Med. Chem. 1986, 29, 2370-2375.
61. 2), A Highly Selective Mu-Opioid Antagonist Peptide, by H-1 and C-13 NMR. Int. J. Pept. Protein Res. 1988, 31, 109-115.
62. Shook, J. E.; Pelton, J.T.; Lemcke, P. K.; Porreca, F.; Hruby, V. J.; Burks, T. F. Mu-Opioid Antagonist Properties of a Cyclic Somatostatin Octapeptide Invivo - Identification of Mu Receptor-Related Functions. J. Pharmacol. Exp. Ther. 1987, 242, 1-7.
63. Kazmierski, W.; Hruby, V. J. A New Approach to Receptor Ligand Design: Synthesis and Conformation of a New Class of Potent and Highly Selective μ Opioid Antagonists Utilizing Tetrahydroisoquinoline Carboxylic Acid. Tetrahedron 1988, 44, 697-710.
64. Kazmierski, W. M.; Yamamura, H. I.; Hruby, V. J. Topographic Design of Peptide Neurotransmitters and Hormones on Stable Backbone Templates: Relation of Conformation and Dynamics to Bioactivity. J. Am. Chem. Soc. 1991, 113, 2275-2283.
65. 10]-Alpha-Melanocyte-Stimulating Hormone: A Cyclic Alpha-Melanotropin Exhibiting Superagonist Biological Activity. Proc. Natl. Acad. Sci. U.S.A. 1982, 79, 1751-1755.
66. Hruby, V. J.; Wilkes, B. C.; Hadley, M. E.; Al-Obeidi, F.; Sawyer, T. K. ; Staples, D. J.; de Vaux, A. E.; Dym, O.; Castrucci, A. M.; Hintz, M. F. Alpha-Melanotropin: The Minimal Active Sequence in the Frog Skin Bioassay. J. Med. Chem. 1987, 30, 2126-2130.
67. 2 - A Topological Model for the Solution Conformation of Alpha-Melanotropin. Biopolymers 1986, 25, 2029-2042.
68. Bauer, W.; Briner, U.; Doepfner, W.; Haller, R.; Huguenin, R.; Marbach, P.; Petcher, T. J.; Pless, J. SMS 201-995 - A Very Potent and Selective Octapeptide Analogue of Somatostatin with Prolonged Action. Life Sci. 1982, 31, 1133-1140.
69. Hruby, V. J.; Han, G. X.; Hadley, M. E. Design and Bioactivities of Melanotropic Peptide Agonists and Antagonists: Design Based on a Conformationally Constrained Somatostatin Template. Lett. Pept. Sci. 1998, 5, 117-120 for preliminary results on some of these peptides.
70. Grieco, P.; Han, G.; Hruby, V. J. New Dimensions in the Design of Potent and Receptor Selective Melanotropin Analogues. In Peptides for the New Millennium, Fields, G. B., Tam, J. P., Barany, G., Eds.; Kluwer Acad. Publ.: Dordrecht, The Netherlands, 2000; pp 541-542.
71. 9 Melanotropin Side Chain Pharmacophores Affects Ligand-Receptor Interactions and Prolonged Biological Activity. J. Med. Chem. 1997, 40, 2740-2749.
72. Haskell-Luevano, C.; Boteju, L. W.; Miwa, H.; Dickinson, C.; Gantz, I.; Yamada, T.; Hadley, M. E.; Hruby, V. J. Topographical Modification of Melanotropin Peptide Analogues with Beta-Methyltryptophan Isomers at Position-9 Leads to Differential Potencies and Prolonged Biological-Activities. J. Med. Chem. 1995, 38, 4720-4729.
73. Schioth, H. B.; Muceniece, R.; Larsson, M.; Mutulis, F.; Szardenings, M. ; Prusis, P.; Lindeberg, G.; Wikberg, J. E. S. Binding of Cyclic and Linear MSH Core Peptides to the Melanocortin Receptor Subtypes. Eur. J. Pharmacol. 1997, 319, 369-373.
74. Al-Obeidi, F.; O'Connor, S. D.; Job, C.; Hruby, V. J.; Pettitt, B. M. NMR and Quenched Molecular Dynamics Studies of Superpotent Linear and Cyclic Alpha-Melanotropins. J. Pept. Res. 1998, 51, 420-431.
75. Lebl, M.; Sugg, E. E.; Hruby, V. J. Proton NMR Spectroscopic Evidence for Sulfur-Aromatic Interactions in Peptides. Int. J. Pept. Protein Res. 1987, 29, 40-45.
76. Hadley, M. E.; Anderson, B.; Heward, C. B.; Sawyer, T. K.; Hruby, V. J. Calcium-Dependent Prolonged Effects on Melanophores of [4-Norleucine, 7-D-Phenylalanine]-α-Melanotropin. Science 1981, 213, 1025-1027.
77. 7]-Alpha-MSH: A Superpotent Melanotropin That "Irreversibly" Activates Melanoma Tyrosinase. Endocr. Res. 1985, 11, 157-170.
78. 7]-Alpha-MSH: A Superpotent Melanotropin with Prolonged Action on Vertebrate Chromatophores. Comp. Biochem. Physiol. A 1985, 81, 1-6.
79. 7]Alpha-MSH. Discovery of a Tripeptidyl Agonist Exhibiting Sustained Bioactivity. Ann. N. Y. Acad. Sci. 1993, 680, 597-599.
80. Kaiser, E.; Colescott, R. I.; Bossinger, C.; Cook, P. I. Color Test for Detection of Free Terminal Amino Groups in Solid-Phase Synthesis of Peptides. Anal. Biochem. 1970, 34, 595-598.
81. Fields, C. G.; Lloyd, D. H.; Macdonald, R. L.; Otteson, K. M.; Noble, R. L. HBTU Activation for Automated Fmoc Solid-Phase Peptide Synthesis. Pept. Res. 1991, 4, 95-101.
82. Schnolzer, M.; Alewood, P.; Jones, A.; Alewood, D.; Kent, S. B. In Situ Neutralization in Boc-Chemistry Solid Phase Peptide Synthesis. Rapid, High Yield Assembly of Difficult Sequences. Int. J. Pept. Protein Res. 1992, 40, 180-193.
83. Ball, H. L.; Mascagni, P. Chemical Synthesis and Purification of Proteins: A Methodology. Int. J. Pept. Protein Res. 1996, 48, 31-47.
84. Adam, S. HBTU - A Mild Activating Agent of Muramic Acid. Bioorg. Med. Chem. Lett. 1992, 2, 571-574.
85. Speicher, A.; Klaus, T.; Eicher, T. O-(1-Benzotriazolyl)-N,N,N′ ,N′-Tetramethyluronium Hexafluorophosphate (HBTU) and O-(7-Aza-1-Benzotriazolyl)-N,N,N′,N′-Tetramethyluronium Hexafluorophosphate (HATU) - Two Modern Peptide Coupling Reagents. J. Prakt. Chem.-Chem. Ztg. 1998, 340, 581-583.
86. Grieco, P.; Gitu, P. M.; Hruby, V. J. Preparation of " Side-Chain-to-Side-Chain" Cyclic Peptides by Allyl and Alloc Strategy: Potentiality for Library Synthesis. J. Pept. Res. 2001, 57, 250-256.
87. Davies, J. S. The Cyclization of Peptides and Depsipeptides. J. Protein Sci. 2003, 471-501.
88. Nomizu, M.; Inagaki, Y.; Yamashita, T.; Ohkubo, A.; Otaka, A.; Fujii, N. ; Roller, P. P.; Yajima, H. Two-Step Hard Acid Deprotection/Cleavage Procedure for Solid-Phase Peptide Synthesis. Int. J. Pept. Protein Res. 1991, 37, 145-152.
89. Beck-Sickinger, A. G.; Schnorrenberg, G.; Metzger, J.; Jung, G. Sulfonation of Arginine Residues as Side Reaction in Fmoc-Peptide Synthesis. Int. J. Pept. Protein Res. 1991, 38, 25-31.
90. Misicka, A.; Hruby, V. J. Optimization of Disulfide Bond Formation. Pol. J. Chem. 1994, 68, 893-899.
91. Shizume, K.; Lerner, A. B.; Fitzpatrick, T. B. In vitro bioassay for the melanocyte stimulating hormone. Endocrinology 1954, 54, 533-560.
92. Wright, R. M.; Lerner, A. B. On the Movement of Pigment Granules in Frog Melanocytes. Endocrinology 1960, 66, 599-609.
93. Huntington, T.; Hadley, M. E. Evidence Against Mass Action Direct Feedback-Control of Melanophore-Stimulating Hormone (MSH) Release. Endocrinology 1974, 95, 472-479.
94. Haskell-Luevano, C.; Rosenquist, A.; Souers, A.; Khong, K. C.; Ellman, J. A.; Cone, R. D. Compounds That Activate the Mouse Melanocortin-1 Receptor Identified by Screening a Small Molecule Library Based Upon the Beta-Turn. J. Med. Chem. 1999, 42, 4380-4387.