Advertisement

Biomedical Polypeptides — A Wellspring of Pharmaceuticals

  • James Samanen

Abstract

Decades of peptide research have created a wide variety of biomedical polypeptides: hormones, neurotransmitters, antigenic protein fragments, synthetic peptides, enzyme substrates and inhibitors, chemotactic agents, and ionophoric agents. A major benefit arising from this research is the creation of a rich source of new pharmocophores from which drugs can be designed.

Regardless of their origin, all peptides address a common group of drug development problems. This chapter reviews some of these problems and the possibilities for development of new drugs from peptides.

The diverse activities of peptides arise from the types of amino acids, from their sequence in the peptide chain, and from the conformations of the peptide backbone. Sequences can be assigned different roles: message sequences, signal sequences, prohormone sequences, and stability sequences. Flexibility of the peptide chain gives rise to many conformations in solution, only a small number of which allow for favorable receptor interaction. Such bioactive conformations can be stabilized in constrained synthetic analogues of the peptide, improving potency, stability, and selectivity.

Although some natural peptides display sufficiently selective action and proteolytic stability to produce therapeutic actions in humans, many more peptides are degraded too rapidly or elicit a multitude of responses on pharmacologic administration. Chemists have discovered a variety of synthetic modifications which can dramatically improve proteolytic stability, potency, and selectivity. A number of synthetic peptides have now been developed which display useful therapeutic actions in humans, many of which can be administered by oral and intranasal routes.

Past research with native peptides developed a strong bias against the potential for either adequate peptide intestinal transport or adequate peptide blood-brain barrier permeability. Recent research suggests that both barriers may be surmountable.

The classic approach to pharmacologic control of endogenous peptide action would be with agonists and antagonists to the peptides. A variety of alternate approaches to control of endogenous peptide levels are offered by the peptide biosynthetic pathway: (1) blockage of posttranslational processing with selective enzyme inhibitors; (2) modulation of peptide release with agonists and antagonists to the natural peptide release factors and to the natural peptide release-inhibiting factors, and with selective enzyme inhibitors to posttranslational processing of these factors; and (3) enhancement of endogenous peptide levels by blocking degradation with selective enzyme inhibitors.

Peptides can also be developed to serve as proteinase inhibitors, synthetic vaccines, and as ionophoric antibiotics.

A wide variety of methods are available for synthesizing peptides of any size or structure: chemical synthesis, biological synthesis, and semisynthesis. In essence, all of the tools are in hand to develop novel therapeutic agents from peptides for both human and animal health maintenance.

Keywords

Vasoactive Intestinal Peptide Peptide Chain Thyrotropin Release Hormone Peptide Analogue Pierce Chemical 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    M. Goodman and R. P. Saltman, Biopolymers 20, 1929–1948 (1981).CrossRefGoogle Scholar
  2. 2.
    M. Bodanszky, Y. S. Klausner, and M. A. Ondetti, Peptide Synthesis, 2nd Edition, Wiley, New York (1976).Google Scholar
  3. 3.
    E. Gross and J. Meienhofer, eds., The Peptides, Analysis Synthesis Biology, Vol. 1, Major Methods of Peptide Bond Formation, Academic Press, New York (1979).Google Scholar
  4. 4.
    E. Gross and J. Meienhofer, eds., The Peptides, Analysis Synthesis Biology, Vol. 2, Special Methods in Peptide Synthesis, Part A, Academic Press, New York (1980).Google Scholar
  5. 5.
    E. Gross and J. Meienhofer, eds., The Peptides, Analysis Synthesis Biology, Vol. 3, Protection of Functional Groups in Peptide Synthesis, Academic Press, New York (1981).Google Scholar
  6. 6.
    M. Bodanszky, Synthesis 5, 333–356 (1981).CrossRefGoogle Scholar
  7. 7.
    R. B. Merrifield and J. M. Stewart, Nature 207, 522–523 (1965).CrossRefGoogle Scholar
  8. 8.
    Spinco Division, Beckman Instruments, Inc., 1050 Page Mill Road, Palo Alto, CA 94304.Google Scholar
  9. 9.
    Vega Biochemicals, 420 East Columbia, Tucson, AZ 85714.Google Scholar
  10. 10.
    Biosearch, Inc., 2980 Kerner Blvd., San Rafael, CA 94901.Google Scholar
  11. 11.
    Peninsula Laboratories, Inc., 611 Taylor Way, Belmont, CA 94002.Google Scholar
  12. 12.
    H. Yajima and N. Fujii,J. Chem. Soc, Chem. Commun. 1980,4 115–116.CrossRefGoogle Scholar
  13. 13.
    D. Yamashiro and C. H. Li, J. Am. Chem. Soc. 100, 5174–5179 (1978).CrossRefGoogle Scholar
  14. 14.
    C. Milstein, Sci. Am., October 1980, 66–74.Google Scholar
  15. 15.
    C. L. Cooney, Science 219, 728–733 (1983).CrossRefGoogle Scholar
  16. 16.
    I. S. Johnson, Science 219, 632–637 (1983).CrossRefGoogle Scholar
  17. 17.
    J. A. Martial, R. A. Mallewell, J. D. Baxter, and H. M. Goodman, Science 205, 602 (1979).CrossRefGoogle Scholar
  18. 18.
    R. A. Hitzeman, D. W. Leung, L. J. Perry, W. J. Kohr, H. L. Levine, and D. V. Goed-del, Science 219, 620–625 (1983).CrossRefGoogle Scholar
  19. 19.
    H. R. B. Pellham and R. J. Jackson, Eur. J. Biochem. 67, 247–256 (1976).CrossRefGoogle Scholar
  20. 20.
    R. E. Offord, in: Semisynthetic Peptides and Proteins (R. E. Offord and C. Di Bello, eds.), pp. 3–19, Academic Press, New York (1978).Google Scholar
  21. 21.
    K. Inouye, K. Watanabe, K. Morihara, Y. Tochino, T. Kanaya, J. Emura, and S. Sakakibara, J. Am. Chem. Soc. 101, 151–152 (1979).CrossRefGoogle Scholar
  22. 22.
    J. P. Greenstein and M. Winitz, in: Chemistry of the Amino Acids, Chapters 1 and 2, Wiley, New York (1961).Google Scholar
  23. 23.
    J. Hughes, T. W. Smith, H. W. Kosteriitz, L. A. Fothergill, B. A. Morgan, and H. R. Norris, Nature 258, 577–579 (1975).CrossRefGoogle Scholar
  24. 24.
    R. Schwyzer, Trends Pharm. Sci. August 1980, 329–331.Google Scholar
  25. 25.
    H. H. Buscher, R. C. Hill, D. Roemer, F. Cardinaux, A. Closse, D. Hauser, and J. Pless, Nature 261, 423–425 (1976).CrossRefGoogle Scholar
  26. 26.
    K. Kangawa, N. Minamino, N. Chino, S. Sakakibara, and H. Matsuo, Biochem. Biophys. Res. Commun. 99, 871–878 (1981).CrossRefGoogle Scholar
  27. 27.
    N. Nimano, K. Kangawa, N. Chino, S. Sakakibara, and H. Matsuo, Biochem. Biophys. Res. Commun. 99, 864–870 (1981).CrossRefGoogle Scholar
  28. 28.
    K. Mizuno, N. Minamino, K. Kangawa, and H. Matsuo, Biochem. Biophys. Res. Commun. 97, 1283–1290 (1980).CrossRefGoogle Scholar
  29. 29.
    D. L. Kirkpatrick, T. Taniguchi, B. N. Jones, A. S. Stern, J. E. Shively, J. Hullihan, S. Kimura, S. Stein, and S. Udenfriend, Proc. Natl. Acad. Sci. U.S.A. 78, 3265–3268 (1981).CrossRefGoogle Scholar
  30. 30.
    B. N. Jones, A. S. Stern, R. V. Lewis, S. Kimura, S. Stein, S. Udenfriend, and J. E. Shively, Arch. Biochem. Biophys. 204, 392–395 (1980).CrossRefGoogle Scholar
  31. 31.
    H. Kakidini, Y. Furutani, H. Takahashi, M. Noda, Y. Morimoto, T. Hirose, M. Asai, S. Inayama, S. Nakanishi, and S. Numa, Nature 298, 245–249 (1982).CrossRefGoogle Scholar
  32. 32.
    A. Goldstein, W. Fischli, L. I. Lowney, M. Hunkapiller, and L. Hood, Proc. Natl. Acad. Sci. U.S.A. 78, 7219–7223 (1981).CrossRefGoogle Scholar
  33. 33.
    C. H. Li, D. Yamashiro, L. -F. Tseng, and H. H. Loh,J. Med. Chem. 20, 325–328 (1977).CrossRefGoogle Scholar
  34. 34.
    P. K. T. Pang, M. C. M. Yang, H. T. Keutmann, and A. D. Kenny, Endocrinology 112, 284–289 (1983).CrossRefGoogle Scholar
  35. 35.
    J. S. Morley, Ann. Rev. Pharmacol. Toxicol. 20, 81–110 (1980).CrossRefGoogle Scholar
  36. 36.
    M. C. Khosla, R. R. Smeby, and F. M. Bumpus, Handbook Exp. Pharmacol. 37, 126–161 (1974).Google Scholar
  37. 37.
    J. E. Mahaffey, M. Rosenblatt, G. L. Shepard, and J. T. Potts, Jr., J. Biol. Chem. 254, 6496–45498 (1979).Google Scholar
  38. 38.
    S. S. Nussbaum, M. Rosenblatt, and J. J. Potts, Jr., J. Biol. Chem. 255, 10,183–10,187 (1980).Google Scholar
  39. 39.
    D. B. Case, H. J. Keim, J. M. Wallace, and J. H. Laragh, Kidney Int. 15, S104–S107 (1979).CrossRefGoogle Scholar
  40. 40.
    A. Zarati, E. S. Canales, I. Sthorey, D. M. Coy, A. M. Comaru-Schally, and A. V. Schally, Contraception 24, 315–320 (1981).CrossRefGoogle Scholar
  41. 41.
    S. Caranikas, J. Mizrahi, E. Escher, and D. Regoli,J. Med. Chem. 25, 1313–1316 (1982).CrossRefGoogle Scholar
  42. 42.
    G. Bloebel, Proc. Natl. Acad. Sci. U.S.A. 77, 1496–1500 (1980).CrossRefGoogle Scholar
  43. 43.
    J. Gainer, P. Gaze, J. -C. Mercier, and B. Robson, Biochemie 62, 231–239 (1982).Google Scholar
  44. 44.
    J. A. Majzoub, M. Rosenblatt, B. Fennick, R. Maunus, H. M. Kronenberg, J. T. Potts, Jr., and J. F. Habener, J. Biol. Chem. 255, 11, 478–11,483 (1980).Google Scholar
  45. 45.
    D. Shields, T. G. Warren, R. F. Green, S. E. Roth, and M. J. Brenner, The Primary Events in the Biosynthesis and Post-Translational Processing of Different Precursors to Somatostatin, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 471–479, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  46. 46.
    J. F. Habener, P. K. Lund, J. W. Jacobs, P. C. Dee, and R. H. Goodman, Polyprotein Precursors of Regulatory Peptides, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 452–467, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  47. 47.
    B. A. Eipper and R. E. Mains, Production of α-N-Acetyl-β-Endorphin (1–26) from α-N-Acetyl-β-Endorphin (1–27), in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 451–456, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  48. 48.
    T. L. O’Donohue and D. M. Dorsa, Peptides 3, 353–395 (1982).CrossRefGoogle Scholar
  49. 49.
    B. H. Frank, J. M. Petter, R. E. Zimmerman, and P. J. Burk, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 729–738, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  50. 50.
    B. M. Austin, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 493–496, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  51. 51.
    J. M. Hambrock, B. A. Morgan, M. J. Rance, and C. F. C. Smith, Nature 262, 782–783 (1976).CrossRefGoogle Scholar
  52. 52.
    K. M. Foley, I. A. Kourides, C. E. Inturrisi, R. F. Kaiko, C. G. Zaroulis, J. B. Posner, R. W. Houde, and C. H. Li, Proc. Natl. Acad. Sci. U.S.A. 76, 5377–5381 (1979).CrossRefGoogle Scholar
  53. 53.
    D. F. Veber, F. W. Holly, W. J. Palaveda, R. F. Nutt, S. J. Bergstrand, M. Torchiana, M. S. Glitzer, R. Saperstein, and R. F. Hirschman, Proc. Natl. Acad. Sci. U.S.A. 75, 2636–2640 (1978).CrossRefGoogle Scholar
  54. 54.
    L. A. La Planche and M. T. Rogers,J. Am. Chem. Soc. 86, 337 (1964).CrossRefGoogle Scholar
  55. 55.
    B. Pullman and A. Pullman, Adv. Protein Chem. 28, 347–526 (1974).CrossRefGoogle Scholar
  56. 56.
    G. N. Ramachandran and V. Sasisekharan, Adv. Protein Chem. 23, 283–437 (1968).CrossRefGoogle Scholar
  57. 57.
    T. N. Bhat, V. Sasisekharan, and M. Vijayan, Int. J. Peptide Protein Res. 13, 170–184 (1979).CrossRefGoogle Scholar
  58. 58.
    F. A. Momany, R. F. McGuire, A. W. Burgess, and H. A. Scheraga, J. Phys. Chem. 79, 2361–2381 (1975).CrossRefGoogle Scholar
  59. 59.
    F. A. Momany,J. Am. Chem. Soc. 98, 2990–2996 (1976).CrossRefGoogle Scholar
  60. 60.
    F. A. Momany,J. Am. Chem. Soc. 98, 2996–3000 (1976).CrossRefGoogle Scholar
  61. 61.
    F. A. Momany,J. Med. Chem. Soc. 21, 63–68 (1978).CrossRefGoogle Scholar
  62. 62.
    V. J. Hruby and H. I. Mosberg, Peptides 3, 329–336 (1982).CrossRefGoogle Scholar
  63. 63.
    H. Koch, Pharm. Int. May 1981, 99–100.Google Scholar
  64. 64.
    Y. Keso, M. Yamaguchi, T. Akita, H. Moritoki, M. Takei, and H. Nakamura, Naturwissenschaften 68, 210–211 (1981).CrossRefGoogle Scholar
  65. 65.
    J. J. Knittel, T. K. Sawyer, V. J. Hruby, and M. E. Hadley, J. Med. Chem. 26, 125–129 (1983).CrossRefGoogle Scholar
  66. 66.
    Chas. R. Baker, Physicians Desk Reference, 36th Edition, Medical Economics Co., Oradell, N.J. (1982), p. 589.Google Scholar
  67. 67.
    Chas. R. Baker, Physicians Desk Reference, 36th Edition, Medical Economics Co., Oradell, N.J. (1982), pp. 799–800.Google Scholar
  68. 68.
    Drugs of the Future 6, 604–606 (1981).Google Scholar
  69. 69.
    I. M. A. Evans, Lancet I, 1232–1233 (1979).CrossRefGoogle Scholar
  70. 70.
    L. A. Austin and H. Heath, N. Eng. J. Med. 304, 269–278 (1978).CrossRefGoogle Scholar
  71. 71.
    T. D. Koelmeyer and E. J. W. Stephens, N. Zeal. Med. J. 87, 434–435 (1978).Google Scholar
  72. 72.
    L. A. Wisneski, W. P. Groom, O. L. Silva, and K. L. Becker, Clin. Pharmacol. Ther. 24, 219–222 (1978).Google Scholar
  73. 73.
    R. Ziegler, H. Minne, J. Hotz, and H. Goebell, Digestion 11, 157–160 (1974).CrossRefGoogle Scholar
  74. 74.
    F. Fracoli, A. Fabri, L. Gnessi, C. Moretti, C. Santoro, and M. Felici, Eur. J. Pharmacol. 78, 381–382 (1982).CrossRefGoogle Scholar
  75. 75.
    A. Papp, Z. Berger, and V. Vacro, Digestion 21, 163–168 (1980).CrossRefGoogle Scholar
  76. 76.
    F. X. Pi-Sunyer, H. R. Kissileff, J. Thornton, and G. P. Smith, Clin. Res. 29, A631 (1981).Google Scholar
  77. 77.
    G. Stacher, H. Bauer, and H. Steinringer, Physiol. Behav. 23, 325–331 (1979).CrossRefGoogle Scholar
  78. 78.
    I. Magnusson and T. Ihre, Lancet I, 792 (1982).CrossRefGoogle Scholar
  79. 79.
    D. Schneider-Helmut, F. Gnirss, M. Monnier, J. Schenker, and G. A. Schonenberger, Int. J. Clin. Pharmacol. Ther. Toxicol. 19, 341–348 (1981).Google Scholar
  80. 80.
    D. H. Catlin, K. K. Hui, H. H. Loh, and C. H. Li, Commun. Psychol. Pharmacol. 1, 493–500 (1977).Google Scholar
  81. 81.
    T. Oyama, S. Fukushi, and T. Jin, Can. Anesth. Soc. J. 29, 24–26 (1982).CrossRefGoogle Scholar
  82. 82.
    T. Oyama, A. Matsuki, T. Taneichi, N. Ling, and R. Guilleman, Am. J. Obstet. Gynecol. 137, 613–616 (1980).Google Scholar
  83. 83.
    D. H. Catlin, K. K. Hui, H. H. Loh, and C. H. Li, Adv. Biochem. Psychopharmacol. 18, 341–350 (1978).Google Scholar
  84. 84.
    Chas. R. Baker, Physicians Desk Reference, 36th Edition, Medical Economics Co., Oradell, N.J. (1982), p. 1001.Google Scholar
  85. 85.
    D. Frasier, G. Castin, B. M. Lippe, T. Aceto, and P. F. Bunger, J. Clin. Endocrinol. Metab. 53, 1213–1217 (1981).CrossRefGoogle Scholar
  86. 86.
    D. Rudman, M. H. Kutner, R. D. Blackstone, R. A. Cushman, R. P. Bain, and J. H. Patterson, N. Engl. J. Med. 305, 123–131 (1981).CrossRefGoogle Scholar
  87. 87.
    Chas. R. Baker, Physicians Desk Reference, 36th Edition, Medical Economics Co., Oradell, N.J. (1982), p. 1842.Google Scholar
  88. 88.
    Chas. R. Baker, Physicians Desk Reference, 36th Edition, Medical Economics Co., Oradell, N.J. (1982), p. 1111.Google Scholar
  89. 89.
    G. Leyendecker, L. Wildt, and M. Hansmann, J. Clin. Endocrinol. Metab. 51, 1214–1216 (1980).CrossRefGoogle Scholar
  90. 90.
    P. Pirazolli, F. Zapparella, F. Bernardi, M. P. Villa, D. Aleksandrowicz, A. Scandola, P. Stancaci, A. Cicognani, and E. Caiccari, Arch. Dis. Childhood 53, 235–238 (1978).CrossRefGoogle Scholar
  91. 91.
    J. Happ, F. Kollmann, C. Kawehl, M. Neubauer, U. Krause, K. Demisch, J. Sandow, W. von Rechenberg, and J. Beyer, Fertil, and Steril. 29, 546–551 (1978).Google Scholar
  92. 92.
    R. H. Ehrensing and A. J. Kastin, Am. J. Psych. 135, 562–566 (1978).Google Scholar
  93. 93.
    R. H. Ehrensing, A. J. Kastin, P. F. Larsens, and G. A. Bishop, Dis. Nervous Syst. 38, 303–307 (1977).Google Scholar
  94. 94.
    A. M. Blackburn, S. R. Bloom, R. G. Cory, D. R. Fletcher, N. D. Christofides, M. L. Fitzpatrick, and J. H. Baron, Lancet I, 987–989 (1980).CrossRefGoogle Scholar
  95. 95.
    Chas. R. Baker, Physicians Desk Reference, 36th Edition, Medical Economics Co., Oradell, N.J. (1982), p. 1689.Google Scholar
  96. 96.
    Chas. R. Baker, Physicians Desk Reference, 36th Edition, Medical Economics Co., Oradell, N.J. (1982), p. 1690.Google Scholar
  97. 97.
    J. Reeve, P. J. Meunier, J. A. Parsons, M. Bernat, O. L. M. Bijovet, P. Courpron, C. Edouard, L. Klenerman, R. M. Neer, J. C. Renier, D. Slovik, F. J. F. E. Vismans, and J. T. Potts, Jr., Brit. Med. J. 1980, 1340–1344.Google Scholar
  98. 98.
    L. Kayasseh, U. Keller, K. Gyr, G. A. Stalder, and M. Wall, Lancet I, 844–845 (1980).CrossRefGoogle Scholar
  99. 99.
    J. P. Galmiche, M. V. Veyroe, and R. Colin, Lancet I, 1306–1307 (1980).Google Scholar
  100. 100.
    B. Limberg and B. Kommerall, Lancet II, 916–917 (1980).CrossRefGoogle Scholar
  101. 101.
    D. B. Case, J. M. Wallace, H. J. Keim, M. A. Weber, J. E. Sealey, and J. H. Laragh, N. Engl. J. Med. 296, 641–646 (1977).CrossRefGoogle Scholar
  102. 102.
    P. Bordigoni, G. Faure, M. C. Bene, M. Dardenne, J. F. Bach, J. Duheille, and D. Olive, Lancet I, 293–297 (1982).CrossRefGoogle Scholar
  103. 103.
    M. T. Lavastida and J. C. Daniels, Fed. Proc. 37, 1669 (1978).Google Scholar
  104. 104.
    J. Costanzi, J. Daniels, G. Thurman, A. Goldstein, and J. Hokanson, Ann. N.Y. Acad. Sci. 332, 148–159 (1979).CrossRefGoogle Scholar
  105. 105.
    P. B. Chretien, S. D. Lipson, R. W. Makuch, D. E. Kenady, and M. H. Cohen, Ann. N.Y. Acad. Sci. 332, 135–147 (1979).CrossRefGoogle Scholar
  106. 106.
    E. M. Veys, E. C. Huskisson, M. Rosenthal, T. L. Vischer, H. Mielants, P. A. Thrower, J. Scott, H. Ott, M. Scheijgord, and J. Symoens, Ann. Rheum. Dis. 41, 441–443 (1982).CrossRefGoogle Scholar
  107. 107.
    J. E. Tyson, U.S. Patent No. 4,125,605 (November 14, 1978).Google Scholar
  108. 108.
    I. Sobue, H. Yamamoto, M. Konagaya, M. Iida, and T. Takayanagi, Lancet I, 418–419 (1980).CrossRefGoogle Scholar
  109. 109.
    D. R. Brown and D. L. Uden, Minn. Med. 62, 427–432 (1979).Google Scholar
  110. 110.
    Drugs of the Future 7, 319–322 (1982).Google Scholar
  111. 111.
    K. Pentella, D. S. Bachman, and C. A. Sandman, Neuropediatric 13, 59–62 (1982).CrossRefGoogle Scholar
  112. 112.
    M. Suzuki, K. Hori, I. Abe, S. Saito, and H. Saito, J. Natl. Cancer Inst. 67, 663–669 (1981).Google Scholar
  113. 113.
    D. B. Case, J. M. Wallace, H. J. Keim, J. E. Sealey, and J. M. Laragh, Am. J. Med. 60, 825–836 (1976).CrossRefGoogle Scholar
  114. 114.
    A. J. Cowley, J. M. Rowley, K. L. Stainer, and J. R. Hampton, Lancet I, 730–732 (1982).Google Scholar
  115. 115.
    R. Di Nicolantorio, F. A. O. Mendelsohn, J.S. Hutchinson, Y. Takata, and A. E. Doyle, Can. J. Physiol. Rev. 242, R498–R504 (1982).Google Scholar
  116. 116.
    J. E. Morley, A. S. Levine, M. M. Oker, M. Grace, and J. Kneip, Peptides 3, 1–6 (1982).CrossRefGoogle Scholar
  117. 117.
    D. Regoli and J. Barabe, Pharmacol. Rev. 32, 1–46 (1980).Google Scholar
  118. 118.
    J.H. Walsh, in: Gut Hormones (S.R. Bloom and J. M. Polak, eds.), pp. 163–170, Churchill Livingstone, New York (1981).Google Scholar
  119. 119.
    M. O. Thorner, J. Rivier, J. Spiess, J.L. Borges, M.L. Vance, S.R. Bloom, A.D. Rogol, M. J. Cronin, D. L. Kaiser, W. S. Evans, J. D. Webster, R. M. MacLeod, and W. Vale, Lancet I, 24–28 (1983).CrossRefGoogle Scholar
  120. 120.
    C. Berquist, S. J. Nillius, and L. Wide, Clin. Endocrinol. 17, 91–98 (1982).CrossRefGoogle Scholar
  121. 121.
    T. Katzorke, D. Propping, M. Vander Ohe, and P. F. Tauber, Fertil, and Steril. 33, 35–42 (1980).Google Scholar
  122. 122.
    O. Levalle, L. Tropea, N. Aparicio, A. Guitelman, A. Manieri, M. Comaru-Schally, and A. V. Schally, Andrologia 13, 207–211 (1981).CrossRefGoogle Scholar
  123. 123.
    G. Tolis, D. Ackman, A. Stellos, A. Mehta, F. Labrie, A. T. A. Fazekas, A. M. Comaru-Schally, and A. V. Schally, Proc. Natl. Acad. Sci. U.S.A. 79, 1658–1662 (1982).CrossRefGoogle Scholar
  124. 124.
    A. R. Hoffman and W. F. Crowley, N. Engl. J. Med. 307, 1237–1241 (1982).CrossRefGoogle Scholar
  125. 125.
    F. Comité, G. B. Cutler, J. Rivier, W. W. Vale, D. L. Loriaux, and W. F. Crowley, N. Engl. J. Med. 305, 1546–1550 (1981).CrossRefGoogle Scholar
  126. 126.
    R. Linde, G. C. Doelle, N. Alexander, F. Kirchner, W. W. Vale, J. Rivier, and D. Rabin, N. Engl. J. Med. 305, 663–667 (1981).CrossRefGoogle Scholar
  127. 127.
    A. Zarati, E. S. Canales, I. Sthorey, D. H. Coy, A. M. Comaru-Schally, and A. V. Schally, Contraception 24, 315–320 (1981).CrossRefGoogle Scholar
  128. 128.
    C. Rivier, J. Rivier, and W. Vale, Science 210, 93–94 (1980).CrossRefGoogle Scholar
  129. 129.
    E. Lederer, J. Med. Chem. 23, 819–825 (1980).CrossRefGoogle Scholar
  130. 130.
    M. Fernstrom, R. E. Carraway, and S. E. Leeman, Frontiers Neuroendocrin. 6, 103–127 (1980).Google Scholar
  131. 131.
    N. E. Gyr, L. Kayasseh, and U. Keller, in: Gut Hormones (S. R. Bloom and J. M. Polak, eds.), pp. 581–585, Churchill Livingstone, New York (1981).Google Scholar
  132. 132.
    A. J. Barnes, R. G. Long, T. E. Adrian, W. Vale, M. R. Brown, J. E. Rivier, J. Hanley, M. A. Ghatei, D. L. Sarson, and S. R. Bloom, Clin. Sci. 61, 653–656 (1981).Google Scholar
  133. 133.
    K. Nishioka, G. F. Bobcock, J. M. Phillips, and R. D. Noyes, Mol. Cell Biochem. 41, 13–18 (1981).CrossRefGoogle Scholar
  134. 134.
    K. Nishioka, Brit. J. Cancer 39, 342–345 (1979).CrossRefGoogle Scholar
  135. 135.
    H. Weingartner, W. Kaye, P. Gold, S. Smallby, R. Petersen, J. C. Gillin, and M. Ebert, Life Sci. 29, 2721–2726 (1981).CrossRefGoogle Scholar
  136. 136.
    P. W. Gold, H. Weingartner, J. C. Bollinger, F. K. Goodwin, and R. M. Post, Lancet I, 992–994 (1979).CrossRefGoogle Scholar
  137. 137.
    I. Kobayashi, Thromb. Res. 16, 775–779 (1979).CrossRefGoogle Scholar
  138. 138.
    F. L. Stassen, R. W. Erickson, W. F. Huffman, J. Stefankiewicz, L. Sulat, and V. D. Wiebelhaus,J. Pharmacol. Exp. Ther. 223, 50–54 (1982).Google Scholar
  139. 139.
    G. Baumann, A. Walser, P. A. Desaulles, F. J. A. Paesi, and L. Geller,J. Clin. Endocrinol. Metab. 42, 60–63 (1976).CrossRefGoogle Scholar
  140. 140.
    D. de Weid, A. Witter, and H. M. Greven, Biochim. Pharmacol. 24, 1463–1468 (1975).CrossRefGoogle Scholar
  141. 141.
    R. J. Vavrek and J. M. Stewart, Peptides 1, 231–235 (1980).CrossRefGoogle Scholar
  142. 142.
    H. J. Showell, R. J. Freer, S. H. Zigmond, E. Schiffmann, S. Aswanikumar, B. A. Corcoran, and E. L. Becker, J. Exp. Med. 143, 1154–1169 (1976).CrossRefGoogle Scholar
  143. 143.
    L. F. Tseng, H. M. Loh, and C. H. Li, Life Sci. 23, 2053 (1978).CrossRefGoogle Scholar
  144. 144.
    D. Roemer, H. H. Buescher, R. C. Hill, J. Pless, W. Bauer, F. Cardinaux, A. Closse, D. Hauser, and R. Huguenin, Nature 268, 547–549 (1977).CrossRefGoogle Scholar
  145. 145.
    H. B. Anderson, B. C. Jorgenson, and A. Engquist, Acta Anaesth. Scand. 26, 69–71 (1982).CrossRefGoogle Scholar
  146. 146.
    E. del Pozo, J. Martin-Perez, A. Stadelmann, J. Girard, and J. Brownell, J. Clin. Invest. 65, 1531–1534(1980).CrossRefGoogle Scholar
  147. 147.
    W. A. Stubbs, G. Delitata, A. Jones, W. J. Jeffcoate, C. R. W. Edwards, S. J. Rotter, G. M. Besser, S. R. Bloom, and K. G. M. M. Alberti, Lancet I, 1225–1227 (1978).CrossRefGoogle Scholar
  148. 148.
    C. Burkhardt, R. C. A. Frederickson, and G. W. Pasternak, Peptides 3, 869–871 (1982).CrossRefGoogle Scholar
  149. 149.
    J. F. Calimlim, W. M. Wardell, K. Sriwatanakul, L. Lasagna, and C. Cox, Lancet I, 1374–1375 (1982).CrossRefGoogle Scholar
  150. 150.
    M. W. Moon, R. A. Lahti, P. F. von Voigtlander, and J. Samanen, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 641–644, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  151. 151.
    J. J. Nestor, Jr., T. L. Ho, R. A. Simpson, B. L. Horner, G. H. Jones, G. I. McRae, and B. H. Vickary, J. Med. Chem. 25, 795–801 (1982).CrossRefGoogle Scholar
  152. 152.
    W. Vale, C. Rivier, and M. Brown, Ann. Rev. Physiol. 39, 473–527 (1977).CrossRefGoogle Scholar
  153. 153.
    J. Botella-Llusia, L. Jaramillo, and A. Charro-Salgado, Acta Obstet. Gynecol. Scand. 56, 337–341 (1977).CrossRefGoogle Scholar
  154. 154.
    D. F. Veber, F. W. Holly, R. F. Nutt, S. J. Bergstrand, S. F. Brady, R. Hirschmann, M. S. Glitzer, and R. Saperstein, Nature (London) 280, 512–514 (1979).CrossRefGoogle Scholar
  155. 155.
    D. F. Veber, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 685–693, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  156. 156.
    G. Metcalf, Brain. Res. Rev. 4, 389–408 (1982).CrossRefGoogle Scholar
  157. 157.
    C. H. Li, J. Blake, and C. H. K. Cheng, Biochem. Biophys. Res. Commun. 102, 697–702 (1981).CrossRefGoogle Scholar
  158. 158.
    D. de Wied, A. Witter, and H. M. Greven, Biochem. Pharmacol. 24, 1463–1468 (1975).CrossRefGoogle Scholar
  159. 159.
    A. W. K. Gaillard and C. A. Varey, Physiol. Behav. 23, 79–84 (1979).CrossRefGoogle Scholar
  160. 160.
    A. N. Nicholson and B. M. Stone, Neuropharmacology 19, 1245–1246 (1980).CrossRefGoogle Scholar
  161. 161.
    B. B. Walker and C. A. Sandman, Am. J. Mental Def 83, 346–352 (1979).Google Scholar
  162. 162.
    J. Turk, P. Needleman, and G. R. Marshall, J. Med. Chem. 18, 1139–1142 (1975).CrossRefGoogle Scholar
  163. 163.
    J. M. van Ree, D. de Wied, W. M. A. Verhoeven, and H. M. van Praag, Lancet I, 1363–1364 (1980).Google Scholar
  164. 164.
    H. M. Emrich, M. Zaudig, W. Kissling, G. Dirlich, D. von Zerssen, and A. Herz, Pharmakopsychiat. Neuropsychopharm. 13, 290–298 (1980).Google Scholar
  165. 165.
    G. Gacel, M. -C. Fournie-Zaluski, and B. P. Roques, FEBS Lett. 118, 245–247 (1980).CrossRefGoogle Scholar
  166. 166.
    B. A. Morgan, J. D. Bower, K. P. Guest, B. K. Handa, G. Metcalf, and C. F. C. Smith, in: Peptides, Proceedings of the Fifth American Peptide Symposium (M. Goodman and J. Meienhofer, eds.), pp. 111–113, Wiley, New York (1977).Google Scholar
  167. 167.
    P. W. Schiller, B. Eggimann, J. Di Maio, C. Lemieux, and J. M. -D. Nguyen, Biochem. Biophys. Res. Commun. 101, 337–343 (1981).CrossRefGoogle Scholar
  168. 168.
    M. I. Mosberg, R. Hurst, V. J. Hruby, J. J. Galligan, T. F. Burks, K. Gee, and H. I. Yamamura, Biochem. Biophys. Res. Commun. 106, 506–512 (1982).CrossRefGoogle Scholar
  169. 169.
    J. DiMaio, T. M. -D. Nguyen, C. Lemieux, and P. W. Schiller, J. Med. Chem. 25, 1432–1438 (1982).CrossRefGoogle Scholar
  170. 170.
    J. D. Bower, B. K. Handa, A. C. Lane, B. A. Morgan, M. J. Rance, C. F. C. Smith, and A. N. A. Wilson, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 607–611, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  171. 171.
    F. A. Momany, C. Y. Bowers, G. A. Reynolds, D. Chang, A. Hong, and K. Newlander, Endocrinology 108, 31–39 (1981).CrossRefGoogle Scholar
  172. 172.
    M. R. Sairan and P. Manurath,J. Biol. Chem. 258, 445–449 (1982).Google Scholar
  173. 173.
    D. H. Coy, I. Mezo, E. Pedroza, M. V. Nekola, J. Vilchey, P. Piyachaturawat, and A. V. Schally, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 775–779, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  174. 174.
    K. Folkers, C. Y. Bowers, F. Momany, and K. J. Friebel, Z. Naturforsch. B 37, 872–876 (1982).Google Scholar
  175. 175.
    W. W. Vale, C. Rivier, M. Perrin, M. Smith, and J. Rivier, in: Neurosecretion and Brain Peptides (J. B. Martin, S. Reichlin, and K. L. Bick, eds.), pp. 609–625, Raven Press, New York (1982).Google Scholar
  176. 176.
    J. Erchegyi, D. H. Coy, M. V. Nekola, E. Pedroza, E. J. Coy, I. Mezo, and A. V. Schally, Peptides 2, 251–253(1981).CrossRefGoogle Scholar
  177. 177.
    P. Lefancier, M. Derrien, X. Jamet, J. Choay, E. Lederer, F. Audibert, M. Parant, F. Parant, and L. Chedid, J. Med. Chem. 25, 85–87 (1982).Google Scholar
  178. 178.
    R. Quirion, F. Rioux, D. Regoli, and S. St. Pierre, Eur. J. Pharmacol. 61, 309–312 (1980).CrossRefGoogle Scholar
  179. 179.
    F. B. Jolicoeur, A. Barbeau, F. Rioux, R. Quirion, and S. St. Pierre, Peptides 2, 171–175 (1981).CrossRefGoogle Scholar
  180. 180.
    G. L. Stahl and R. Walter, J. Med. Chem. 20, 492–495 (1977).CrossRefGoogle Scholar
  181. 181.
    N. Cort, S. Einarsson, and S. Viring, Am. J. Vet. Res. 40, 430–432 (1979).Google Scholar
  182. 182.
    Z. Veznik, A. Holub, Z. Zraly, V. Kummer, V. Holcak, K. Jost, and J. H. Cort, Am. J. Vet. Res. 40, 425–429 (1979).Google Scholar
  183. 183.
    V. J. Hruby, K. K. Deb, D. M. Yamamoto, M. E. Hadley, and W. Y. Chan,J. Med. Chem. 22, 7–12 (1979).CrossRefGoogle Scholar
  184. 184.
    V. J. Hruby, H. I. Mosberg, M. E. Hadley, W. Y. Chan, and A. M. Powell, Int. J. Peptide Protein Res. 16, 372–381 (1980).CrossRefGoogle Scholar
  185. 185.
    J. Lowbridge, M. Manning, J. Seto, J. Haldar, and W. H. Sawyer,J. Med. Chem. 22, 565–569 (1979).CrossRefGoogle Scholar
  186. 186.
    W. H. Sawyer, J. Haldar, D. Gazis, J. Seto, K. Bankowski, J. Lowbridge, A. Turan, and M. Manning, Endocrinology 106, 80–91 (1980).CrossRefGoogle Scholar
  187. 187.
    J. L. Fries, W. A. Murphy, J. Suieras-Dias, and D. H. Coy, Peptides 3, 811–814 (1982).CrossRefGoogle Scholar
  188. 188.
    W. Bauer, U. Briner, W. Doepfner, R. Haller, R. Hugeinin, P. Marbach, T. J. Petcher, and J. Pless, Life Sci. 31, 1130–1140 (1982).CrossRefGoogle Scholar
  189. 189.
    R. Maurer, B. H. Gaehwiler, H. H. Buscher, R. C. Hill, and D. Roemer, Proc. Natl. Acad. Sci. U.S.A. 79, 4815–4817 (1982).CrossRefGoogle Scholar
  190. 190.
    V. M. Garsky, J. Bicksler, R. L. Fenichel, and E. L. Lien, in: Peptides, Proceedings of the Fifth American Peptide Symposium (M. Goodman and J. Meienhofer, eds.), pp. 547–550, Wiley, New York (1977).Google Scholar
  191. 191.
    C. A. Meyers, D. H. Coy, W. A. Murphy, J. W. Redding, A. Arimura, and A. V. Serially, Proc. Natl. Acad. Sci. U.S.A. 77, 577–579 (1980).CrossRefGoogle Scholar
  192. 192.
    F. J. Bex, A. Corben, D. Sarantakis, and E. Lien, Nature 284, 342–343 (1980).CrossRefGoogle Scholar
  193. 193.
    Y. Harano, H. Hidaka, T. Nakano, J. Emura, T. Kimura, S. Sakakibara, and Y. Shigeta, Biomed. Res. 1, 560–564 (1980).Google Scholar
  194. 194.
    K. Folkers, J. Horig, G. Rampold, P. Lane, S. Rosell, and U. Bjorkroth, Acta Chem. Scand. B 36, 389–395 (1982).CrossRefGoogle Scholar
  195. 195.
    S. Caranikas, J. Mizrahi, E. Escher, and D. Regoli,J. Med. Chem. 25, 1313–1316 (1982).CrossRefGoogle Scholar
  196. 196.
    M. Fridkin, Y. Stabinsky, V. Zakuth, and Z. Spirer, Biochim. Biophys. Acta 496, 203–211 (1977).CrossRefGoogle Scholar
  197. 197.
    N. Fukuda, O. Nishimura, M. Shikato, C. Hatanaka, M. Miyamoto, Y. Saji, R. Nakayama, M. Fujino, and Y. Nagawa, Chem. Pharm. Bull. 28, 1667–1672 (1980).CrossRefGoogle Scholar
  198. 198.
    R. F. Nutt, F. W. Holly, C. Homnick, R. Hirschmann, D. F. Veber, and B. H. Arison, J. Med. Chem. 24, 692–698 (1981).CrossRefGoogle Scholar
  199. 199.
    G. Metcalf, D. W. Dettmar, A. G. Lynn, D. Brewster, and M. E. Havler, Regul. Peptides 2, 277–284 (1981).CrossRefGoogle Scholar
  200. 200.
    D. R. Brown and D. L. Uden, Minn. Med. 62, 427–432 (1979).Google Scholar
  201. 201.
    F. Laczi, G. Mezei, J. Julesz, and F. A. Faszlo, Int. J. Clin. Pharmacol. Ther. Toxicol. 18, 63–68 (1980).Google Scholar
  202. 202.
    C. R. Botos, C. W. Smith, Y. L. Chen, and R. Walter,J. Med. Chem. 22, 926–935 (1979).CrossRefGoogle Scholar
  203. 203.
    C. W. Smith, C. R. Botos, and R. Walter, in: Peptides, Proceedings of the Fifth American Peptide Symposium (M. Goodman and J. Meienhofer, eds.), pp. 161–164, Wiley, New York (1977).Google Scholar
  204. 204.
    C. W. Smith and R. Walter, Science 199, 297–298 (1978).CrossRefGoogle Scholar
  205. 205.
    D. A. Jones, Jr. and W. H. Sawyer, J. Med. Chem. 23, 696–698 (1980).CrossRefGoogle Scholar
  206. 206.
    M. Manning, B. Lammek, M. Kruszynski, J. Seto, and W. H. Sawyer, J. Med. Chem. 25, 408–414 (1982).CrossRefGoogle Scholar
  207. 207.
    M. Manning, W. A. Klis, A. Olma, J. Seto, and W. H. Sawyer,J. Med. Chem. 25, 414–419 (1982).CrossRefGoogle Scholar
  208. 208.
    D. W. Cheesman, R. Schlegel, A. M. Sugasay, and P. H. Forsham, Endocrinology 112, 269–276 (1983).CrossRefGoogle Scholar
  209. 209.
    H. P. J. Bennett and C. McMartin, Pharmacol Rev. 30, 347–392 (1978).Google Scholar
  210. 210.
    F. A. Carone, P. R. Peterson, and G. Flouret, J. Lab. Chem. Med. 100, 1–14 (1982).Google Scholar
  211. 211.
    J. S. Morley, Trends in Pharm. Sci. December 1980, 463–168.Google Scholar
  212. 212.
    A. F. Spatola, in: Chemistry and Biochemistry of Amino Acids, Peptides and Proteins (B. Weinstein, ed.), Marcel Dekker, New York (1983) (in press).Google Scholar
  213. 213.
    M. M. Hahn, P. O. Sammes, P. D. Kennewell, and J. B. Taylor,J. Chem. Soc, Chem. Commun. 1980, 234–235.Google Scholar
  214. 214.
    M. T. Cox, J. J. Gormley, C. F. Hayward, and N. N. Petter, J. Chem. Soc, Chem. Commun. 1980, 800–802.Google Scholar
  215. 215.
    M. Szelke, B. Leckie, A. Hallett, D. M. Jones, J. Suciras, B. Atrash, and A. F. Lever, Nature 299, 255 (1982).CrossRefGoogle Scholar
  216. 216.
    G. Van Lommen, F. Al-Obeidi, E. Delock, E. Destrijker, G. van Binst, and V. J. Hruby, in: Peptides 1980, Proceedings of the 16th European Peptide Symposium (K. Brunfeldt, ed.), pp. 248–252, Scriptor, Copenhagen (1981).Google Scholar
  217. 217.
    J. T. Shaw, L. Miller, M. J. Turnbull, J. T. Gormley, and J. S. Morley, Life Sci. 31, 1259 (1982).CrossRefGoogle Scholar
  218. 218.
    A. F. Spatola and A. L. Betto, J. Org. Chem. 46, 2393–2394 (1981).CrossRefGoogle Scholar
  219. 219.
    S. L. Baxter and J. S. Bradshaw,J. Org. Chem. 46, 831–832 (1981).CrossRefGoogle Scholar
  220. 220.
    C. B. Pert, D. L. Bowie, B. T. W. Fong, and J. -K. Chang, Opiates and Endogenous Opioid Peptides, Elsevier/North-Holland Biomedical Press, Amsterdam (1976), pp. 79–86.Google Scholar
  221. 221.
    V. J. Hruby, Life Sci. 31, 189–199 (1982).CrossRefGoogle Scholar
  222. 222.
    M. J. O’Donnell, B. Le Cleff, D. B. Rusterholtz, L. Ghosez, J. -P. Antoine, and M. Navarro, Tetrahedron Lett. 23, 4259–4262 (1982).CrossRefGoogle Scholar
  223. 223.
    K. Stachowiak, M. C. Khosla, K. Placinska, P. A. Khairallah, and F. M. Bumpus,J. Med. Chem. 22, 1128–1130 (1979).CrossRefGoogle Scholar
  224. 224.
    Y. Shimohigushi, M. L. English, C. H. Stammer, and R. Costa, Biochem. Biophys. Res. Commun. 104, 583–590 (1982).CrossRefGoogle Scholar
  225. 225.
    R. Kalir and A. Patchornik, Polym. Lett. Edit. 16, 35–39 (1978).CrossRefGoogle Scholar
  226. 226.
    M. Chorev, R. Shavitz, M. Goodman, S. Minick, and R. Guillemin, Science 204, 1210 (1979).CrossRefGoogle Scholar
  227. 227.
    N. Izumiya, T. Kato, H. Aoyagi, M. Waki, and M. Kondo, Synthetic Aspects of Biologically Active Cyclic Peptides — Gramicidin S and Tyrocidines, Halsted Press/Wiley, New York (1979).Google Scholar
  228. 228.
    G. Metcalf, Pharm. J. 1979, 356–358.Google Scholar
  229. 229.
    D. Hudson, R. Sharpe, and M. Szelke, Int. J. Peptide Protein Res. 15, 122–129 (1980).CrossRefGoogle Scholar
  230. 230.
    M. M. Hann, P. G. Sammes, P. D. Kennewell, and J. B. Taylor, J. Chem. Soc, Chem. Commun. 1980, 234–235.Google Scholar
  231. 231.
    D. H. Coy and A. J. Kastin, Pharmacol. Ther. 10, 657–668 (1980).CrossRefGoogle Scholar
  232. 232.
    J. Pless, W. Bauer, F. Cardinaux, A. Closse, D. Hauser, R. Huguenin, D. Roemer, H. H. Buescher, and R. C. Hill, Helv. Chim. Acta 62, 398–411 (1979).CrossRefGoogle Scholar
  233. 233.
    R. C. A. Frederickson, E. L. Smithwick, and R. Shuman, in: Characteristics and Functions of Opioids (J. M. Van Ree and L. Terinius, eds.), pp. 215–216, Elsevier North-Holland Biomedical Press, Amsterdam (1978).Google Scholar
  234. 234.
    C. R. Beddell, R. B. Clark, G. W. Hardy, C. A. Lowe, F. B. Ubatuba, J. R. Vane, F. R. S. Wilkinson, S. Wilkinson, K. -J. Chang, P. Cuatrecasas, and R. J. Miller, Proc. R. Soc. London, Ser B 198, 249–265 (1977).CrossRefGoogle Scholar
  235. 235.
    J. Di Maio and P. W. Schiller, Proc. Natl. Acad. Sci. U.S.A. 77, 7162–7166 (1980).CrossRefGoogle Scholar
  236. 236.
    A. S. Dutta, J. J. Gormley, C. F. Hayward, J. J. Morley, J. S. Shaw, G. J. Stacey, and M. J. Turnbull, Acta Pharm. Suec. Suppl. 14, 14–15 (1977).Google Scholar
  237. 237.
    J. F. Calimlim, W. M. Wardell, K. Sriwatanakul, L. Lasagna, and C. Cox, Lancet I, 1374–1375 (1982).CrossRefGoogle Scholar
  238. 238.
    R. C. A. Fredenckson, E. L. Smithwick, and D. P. Henry, in: Neuropeptides and Neural Transmission (C. A. Marson and W. Z. Traczyk, eds.), pp. 227–235, Raven Press, New York (1980).Google Scholar
  239. 239.
    G. Stacher, P. Bauer, H. Steinringer, E. Schrieber, and G. Schmierer, Pain 7, 159–172 (1979).CrossRefGoogle Scholar
  240. 240.
    M. R. Boarder, E. Erdelyi, and J. D. Barchas, Biochem. Pharmacol. 30, 1289–1293 (1981).CrossRefGoogle Scholar
  241. 241.
    K. Inouye, K. Watanabe, Y. Tochino, M. Kobayashi, and Y. Shigeta, Biopolymers 20, 1845–1850 (1981).CrossRefGoogle Scholar
  242. 242.
    K. Bauer, Degradation of Neuropeptides, in: Brain and Pituitary Peptides, Ferring Symposium, Munich, 1979 (W. Wuttke, A. Weindl, K. H. Voigt, and R. R. Dries, eds.), pp. 213–222, Karger, Basel (1980).Google Scholar
  243. 243.
    J. W. Taylor, R. J. Miller, and E. T. Kaiser, Mol. Pharmacol. 22, 657–666 (1982).Google Scholar
  244. 244.
    D. Brewster, P. W. Dettmar, and G. Metcalf, Neuropharmacology 20, 497–503 (1981).CrossRefGoogle Scholar
  245. 245.
    J. M. Stewart, M. E. Hall, J. Harkins, R. C. A. Frederickson, L. Terenius, T. Hokfeldt, and W. A. Krivoy, Peptides 3, 851–857 (1982).CrossRefGoogle Scholar
  246. 246.
    A. B. Zinn, J. J. Plantner, and D. M. Carlson, in: The Glycoconjugates, Vol. 1, Mammalian Glycoproteins and Glycolipids (M. I. Horowitz and W. Pigman, eds.), pp. 69–85, Academic Press, New York (1977).Google Scholar
  247. 247.
    K. -J. Chang and P. Cuatrecasas, Fed. Proc. 40, 2729–2734 (1981).Google Scholar
  248. 248.
    D. S. Kemp and E. T. Sun, Tetrahedron Lett. 23, 3759–3760 (1982).CrossRefGoogle Scholar
  249. 249.
    P. C. Belanger, C. Dufresne, J. Scheigetz, R. N. Young, J. P. Springer, and G. I. Dmitrienko, Can. J. Chem. 60, 1019–1029 (1982).CrossRefGoogle Scholar
  250. 250.
    J. L. Krstenansky, R. L. Baranowski, and B. L. Currie, Biochem. Biophys. Res. Commun. 109, 1368–1374 (1982).CrossRefGoogle Scholar
  251. 251.
    R. M. Freidinger, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 673–683, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  252. 252.
    P. M. Conn, D. C. Rogers, J. M. Stewart, J. Niedel, and T. Sheffield, Nature 296, 653–656 (1982).CrossRefGoogle Scholar
  253. 253.
    R. Schwyzer and V. M. Kriwaczek, Biopolymers 20, 2011–2020 (1981).CrossRefGoogle Scholar
  254. 254.
    L. Chedid, M. Parant, F. Parant, F. Audibert, F. Lefrancier, J. Choay, and M. Sela, Proc. Natl. Acad. Sci. U.S.A. 76, 6557–6561 (1979).CrossRefGoogle Scholar
  255. 255.
    T. Costa, Y. Shimohigashi, S. A. Krumins, P. J. Munson, and D. Rodbard, Life Sci. 31, 1625–1632 (1982).CrossRefGoogle Scholar
  256. 256.
    D. B. A. Silk and A. M. Dawson, Int. Rev. Physiol. Gastroint. Physiol. III 19, 153–204 (1979).Google Scholar
  257. 257.
    D. M. Matthews and S. A. Adibi, Gastroenterology 71, 151–161 (1976).Google Scholar
  258. 258.
    W. Veatch, S. Weinstein, B. A. Wallace, and E. R. Blout, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 635–638, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  259. 259.
    E. Bamberg, H. -J. Appell, H. Alpes, and P. Lauger, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 629–638, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  260. 260.
    G. Boheim and H. A. Kolb,J. Membr. Biol. 38, 99–150 (1978).CrossRefGoogle Scholar
  261. 261.
    I. L. Karle, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 681–690, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  262. 262.
    C. M. Deber, P. D. Adawadkar, M. E. M. Young, and J. Tom-Kun, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 691–694, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  263. 263.
    B. A. Wallace and E. R. Blout, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 697–698, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  264. 264.
    D. B. A. Silk, Clin. Sci. 60, 607–615 (1981).Google Scholar
  265. 265.
    A. L. Warshaw, W. A. Walker, and K. J. Isselbacher, Gastroenterology 66, 987–992 (1974).Google Scholar
  266. 266.
    M. A. Stelzter-Stevenson, F. Carone, G. Flouret, and D. Peterson, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 821–824, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  267. 267.
    H. Gainer, ed., Peptides in Neurobiology, Plenum Press, New York (1977).Google Scholar
  268. 268.
    A. J. Kastin, L. A. Wade, D. H. Coy, A. V. Schally, and R. D. Olson, in: Brain and Pituitary Peptides, Ferring Symposium, Munich, 1979 (W. Wuttke, A. Weindl, K. H. Voight, and R. -R. Dries, eds.), pp. 71–78, Karger, Basel (1980).Google Scholar
  269. 269.
    R. E. Miller and N. Ogawa, J. Comp. Physiol. Psychol. 55, 211–213 (1962).CrossRefGoogle Scholar
  270. 270.
    A. Pfefferbaum, P. A. Berger, G. R. Elliott, J. R. Tinklenberg, B. S. Kopell, J. D. Barchas, and C. H. Li, Psych. Res. 1, 83–88 (1979).CrossRefGoogle Scholar
  271. 271.
    D. A. Gorelich, D. M. Catlin, and R. H. Gerner, Mod. Problems: Pharmacopsych. 17, 236–245 (1981).Google Scholar
  272. 272.
    R. L. Moss and S. M. McCann, Science 181, 177–179 (1973).CrossRefGoogle Scholar
  273. 273.
    A. J. Kastin, L. H. Miller, D. Gonzalez-Barcena, W. D. Hawley, K. Dyster-Aas, A. V. Schally, M. L. Velasco-Parra, and M. Velasco, Physiol. Behav. 7, 893–896 (1971).CrossRefGoogle Scholar
  274. 274.
    H. Weingartner, P. Gold, J. L. Ballinger, S. A. Smallberg, R. Summers, D. R. Rubinow, R. M. Post, and F. K. Goodwin, Science 211, 601–603 (1981).CrossRefGoogle Scholar
  275. 275.
    W. H. Oldendorf, Exp. Eye Res. 1977 Suppl, 177–190.Google Scholar
  276. 276.
    W. H. Oldendorf, Peptides 2, 109–111 (1981).CrossRefGoogle Scholar
  277. 277.
    A. J. Kastin, C. Nissen, and D. H. Coy, Pharmacol. Biochem. Behav. 15, 955–959 (1981).CrossRefGoogle Scholar
  278. 278.
    C. Crane, in: Ion Homeostasis of the Brain, (B. K. Siesjo and S. C. Sorensen, eds.), pp. 52–62, Munksgaard, Copenhagen (1971).Google Scholar
  279. 279.
    R. H. Gerner, B. Sharp, and D. H. Catlin,J. Clin. Endocrinol. Metab. 55, 358–360 (1982).CrossRefGoogle Scholar
  280. 280.
    D. A. Gorelich, D. H. Catlin, and R. M. Greene, Mod. Problems: Pharmacopsych. 17, 236–245 (1981).Google Scholar
  281. 281.
    T. Oyama, S. Fukushi, and T. Jin, Can. Anaesth. Soc. J. 29, 24–26 (1982).CrossRefGoogle Scholar
  282. 282.
    D. H. Catlin, K. K. Hui, H. H. Loh, and C. H. Li, Commun. Psycho. Pharmacol. 1, 493–500 (1977).Google Scholar
  283. 283.
    W. M. Pardridge, H. J. L. Frank, E. M. Cornford, L. D. Braun, P. D. Crane, and W. H. Oldendorf, in: Neurosecretion and Brain Peptides (J. B. Martin, S. Reichlin, and K. L. Bick, eds.), Raven Press, New York (1981).Google Scholar
  284. 284.
    M. van Houten, E. L. Schiffrin, J. F. E. Mann, B. I. Posner, and R. Boucher, Brain Res. 186, 480–485 (1980).CrossRefGoogle Scholar
  285. 285.
    R. Bergland, H. Blume, A. Hamilton, P. Monica, and R. Peterson, Science 31, 541–543 (1980).CrossRefGoogle Scholar
  286. 286.
    D. M. Dorsa, E. R. de Kloet, E. Mezey, and D. de Wied, Endocrinology 104, 1663–1666 (1979).CrossRefGoogle Scholar
  287. 287.
    B. A. Shoelkens, R. Lux, and R. Steinbach, Arch. Int. Pharmacodyn. 229, 244–250 (1977).Google Scholar
  288. 288.
    Drugs of the Future 7, 319–322 (1982).Google Scholar
  289. 289.
    K. Pentella, D. S. Bachman, and C. A. Sandman, Neuropediatrics 13, 59–62 (1982).CrossRefGoogle Scholar
  290. 290.
    J. Fox, Chem. Eng. News, April 21, 1980, 27–28.Google Scholar
  291. 291.
    G. Bylinsky, The Battle for America’s Sweet Tooth, Fortune (July 26, 1982), pp. 28–32.Google Scholar
  292. 292.
    H. R. Brunner, H. Gavras, B. Waeber, G. A. Turini, and J. P. Wauters, in: Captopril and Hypertension (D. B. Case, E. H. Sonnenblick, and J. H. Laragh, eds.), pp. 149–170, Plenum Medical Book Co., New York, 1980.Google Scholar
  293. 293.
    A. J. Cowley, K. L. Stainer, J. M. Rowley, and J. R. Hampton, Lancet II, 730–732 (1982).CrossRefGoogle Scholar
  294. 294.
    C. S. Sweet, D. M. Gross, P. T. Arbegast, S. L. Gaul, P. M. Britt, C. T. Ludden, D. Weitz, and C. A. Stone, J. Pharmcol. Exp. Ther. 216, 558–566 (1981).Google Scholar
  295. 295.
    L. Chedid, F. Audibert, P. Lefrancier, J. Choay, and E. Lederer, Proc. Natl. Acad. Sci. U.S.A. 73, 2472–2475 (1976).CrossRefGoogle Scholar
  296. 296.
    G. Gregoriadis, Drug 29, 261–266 (1982).CrossRefGoogle Scholar
  297. 297.
    G. Dapergolas and G. Gregoriadis, Lancet I, 824–827 (1976).CrossRefGoogle Scholar
  298. 298.
    J. F. Arieta-Molero, K. Aleck, M. K. Sinha, C. M. Brownscheidle, L. J. Shapiro, and M. A. Sperling, Hormone Res. 16, 249–256 (1982).CrossRefGoogle Scholar
  299. 299.
    S. Papaioannou, P. -C. Yang, and R. Novoteny, Clin. Exp. Hypertension 1, 407–422 (1978).CrossRefGoogle Scholar
  300. 300.
    T. J. Postmes, M. Hukkelhoven, A. E. J. M. Vanden Bogaard, S. G. Haiders, and J. Loenegracht, J. Pharm. Pharmacol. 32, 722–724 (1980).CrossRefGoogle Scholar
  301. 301.
    A. J. Schroit and I. J. Fidler, Cancer Res. 42, 161–167 (1982).Google Scholar
  302. 302.
    W. Lotz and B. Syllwasschy,J. Pharm. Pharmacol. 31, 649–650 (1979).CrossRefGoogle Scholar
  303. 303.
    S. Futaguchi, K. Odaguchi, A. Tanaka, and M. Hirata,J. Pharm. Pharmacol. 34, 343–344 (1982).CrossRefGoogle Scholar
  304. 304.
    A. Zaffaroni, Delivering drugs, CHEMTECH, February 1980, 82–88.Google Scholar
  305. 305.
    W. F. Ganong, Review of Medical Physiology, 10th Edition, Lange Med. Pub., Los Altos, Calif. (1981), pp. 329–330.Google Scholar
  306. 306.
    J. H. Walsh, in: Gut Hormones (S. R. Bloom and J. M. Pollak, eds.), pp. 163–170, Churchill Livingstone, New York (1981).Google Scholar
  307. 307.
    J. H. Laragh, in: Captopril and Hypertension (D. B. Case, E. H. Sonnenblick, and J. H. Laragh, eds.), pp. 73–184, Plenum Medical Book Col., New York (1980).Google Scholar
  308. 308.
    B. Kiel, in: Proteases and Hormones (M. K. Agarwall, ed.), pp. 1–18, Elsevier/North-Holland Biomedical Press, New York (1979).Google Scholar
  309. 309.
    L. T. Skeggs, F. E. Dorer, M. Levine, K. E. Lenty, and J. R. Kahn, Adv. Exp. Med. Biol. 130, 1–23 (1978).Google Scholar
  310. 310.
    W. S. Peart, in: Captopril and Hypertension (D. B. Case, E. H. Sonnenblick, and J. H. Laragh, eds.), pp. 39–56, Plenum Medical Book Co., New York (1980).Google Scholar
  311. 311.
    E. Haber and J. Burton, Fed. Proc. 38, 2768–2773 (1979).Google Scholar
  312. 312.
    J. Burton, R. J. Cody, Jr., J. A. Herd, and E. Haber, Proc. Natl. Acad. Sci. U.S.A. 77, 5476–5479 (1980).CrossRefGoogle Scholar
  313. 313.
    D. W. Cushman, H. S. Cheung, E. F. Sabo, B. Rubin, and M. A. Ondetti, Fed. Proc. 38, 2778–2782 (1979).Google Scholar
  314. 314.
    J. Biollaz, M. Burnier, G. A. Turin, D. B. Brunner, M. Porchet, H. J. Gomez, F. H. Jones, F. Ferber, W. B. Abrams, H. Gavras, and H. R. Brunner, Clin. Pharmacol. Ther. 29, 665–670 (1981).CrossRefGoogle Scholar
  315. 315.
    T. Hata, T. Ogihara, M. Nakamura, S. Gotoh, K. Masuo, S. Saeki, A. Kumagai, and Y. Kumahara, Eur. J. Clin. Pharmacol. 23, 7–10 (1982).CrossRefGoogle Scholar
  316. 316.
    T. Kono, F. Ikeda, F. Oseko, Y. Ohmori, R. Nakano, H. Muranaka, A. Taniguchi, H. Imura, M. C. Khosla, and F. M. Bumpus, Acta Endocrinol. 99, 577–584 (1982).Google Scholar
  317. 317.
    W. F. Ganong, Review of Medical Physiology, 10th Edition, Lange Med. Pub., Los Altos, Calif. (1981).Google Scholar
  318. 318.
    W. B. Wehrenberg, N. Ling, P. Brazeau, F. Esch, P. Bohlen, A. Baird, S. Ying, and R. Guillemin, Biochem. Biophys. Res. Commun. 109, 382–387 (1982).CrossRefGoogle Scholar
  319. 319.
    R. P. Millar, L. J. Klaff, J. Barron, N. S. Levitt, and N. Ling, Clin. Endocrinol 17, 103–107 (1982).CrossRefGoogle Scholar
  320. 320.
    W. Vale, P. Brazeau, C. Rivier, J. Rivier, G. Grant, R. Burgus, and R. Guillemin, Fed. Proc. 32, 211–214(1973).Google Scholar
  321. 321.
    Gut Hormones, (S. R. Bloom and J. M. Polak, eds.), Churchill Livingstone, New York (1981).Google Scholar
  322. 322.
    N. Bethege, F. Diel, and K. H. Usadel, J. Clin. Chem. Clin. Biochem. 20, 603–613 (1982).Google Scholar
  323. 323.
    H. Yajima, H. Ogawa, H. Ueda, and H. Takagi, Chem. Pharm. Bull. 28, 1935–1938 (1980).CrossRefGoogle Scholar
  324. 324.
    B. Malfroy, J. P. Swartz, A. Guyon, B. P. Roques, and J. -C. Schwartz, Nature 276, 523–526 (1978).CrossRefGoogle Scholar
  325. 325.
    B. P. Roques, M. C. Fournie-Zaluski, E. Soroca, J. M. Lecomte, B. Malfroy, C. Llorens, and J. -C. Schwartz, Nature 288, 286–288 (1980).CrossRefGoogle Scholar
  326. 326.
    B. Rubin, M. J. Antonaccio, and Z. P. Horovitz, in: Captopril and Hypertension (D. B. Case, E. H. Sonnenblick, and J. H. Laragh, eds.), pp. 115–135, Plenum Medical Book Co., New York (1980).Google Scholar
  327. 327.
    A. J. Barrett, in: Enzyme Inhibitors as Drugs (M. Sandler, ed.), pp. 219–229, MacMillan Press, London (1980).Google Scholar
  328. 328.
    L. Zaneveld, R. Robertson, and W. Williams, FEBS Lett. 11, 345–347 (1970).CrossRefGoogle Scholar
  329. 329.
    P. Libby and A. L. Goldberg, Science N.Y. 199, 534–536 (1978).CrossRefGoogle Scholar
  330. 330.
    A. Stracher, E. B. McGowan, and S. A. Shafig, Science N.Y. 200, 50–51 (1978).CrossRefGoogle Scholar
  331. 331.
    J. Kleinerman, V. Ranga, D. Rynbrandt, M. P. C. Ip, J. Sorensen, and J. C. Powers, Am. Rev. Resp. Dis. 121, 381–387 (1980).Google Scholar
  332. 332.
    A. Janoff and R. Dearing, Am. Rev. Resp. Dis. 121, 1024–1025 (1980).Google Scholar
  333. 333.
    S. Bajusz, E. Barabas, P. Tolnay, E. Szell, and D. Bagdy, Int. J. Peptide Protein Res. 12, 217–221 (1978).CrossRefGoogle Scholar
  334. 334.
    H. Umezawa, J. Antibiot. 30 (Suppl.), 138–163 (1977).CrossRefGoogle Scholar
  335. 335.
    R. A. Lerner, Synthetic vaccines, Sci. Am., February 1983, 66–74.Google Scholar
  336. 336.
    R. F. Peterson, Ann. Clin. Res. 14, 245–252 (1982).Google Scholar
  337. 337.
    J. Beale, Nature 298, 14–15 (1982).CrossRefGoogle Scholar
  338. 338.
    G. R. Marshall and T. M. Balasubramanian, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 639–646, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  339. 339.
    G. Jung, H. Bruckner, R. Oekonomopulos, G. Boheim, E. Breitmaier, and W. K. Konig, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 647–654, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  340. 340.
    N. Izumiya, T. Kato, H. Aoyagi, M. Waki, and M. Kondo, in: Synthetic Aspects of Biologically Active Cyclic PeptidesGramicidin S and Tyrocidines, pp. 99–108, Halsted Press/Wiley, New York (1979).Google Scholar
  341. 341.
    B. F. Gisin, D. G. Davis, J. A. Hamilton, M. N. Sabeson, and L. K. Steinrauf, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 711–714, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  342. 342.
    D. G. Davis and B. F. Gisin, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptide Symposium (E. Gross and J. Meienhofer, eds.), pp. 719–722, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  343. 343.
    W. Veatch, N. Sarker, P. K. Mukherjee, D. Langley, H. Paulus, V. T. Ivanov, and E. N. Shepel, in: Peptides, Structure and Biological Function; Proceedings of the Sixth American Peptides Symposium (E. Gross and J. Meienhofer, eds.), pp. 707–710, Pierce Chemical Co., Rockford, Ill. (1979).Google Scholar
  344. 344.
    S. G. Laland, T. -L. Zimmer, and O. Froyshou, in: Bioactive Peptides Produced by Microorganisms (M. Umezawa, T. Takita, T. Shiba, eds.), pp. 7–34, Halsted Press/Wiley, New York (1978).Google Scholar
  345. 345.
    E. Schiffman, H. J. Showell, B. A. Corcoran, P. A. Ward, E. Smith, and E. L. Becker, J. Immunol. 144, 1831–1837 (1975).Google Scholar
  346. 346.
    Y. Yamasaki and K. Maekawa, Agric. Biol. Chem. (Tokyo) 42, 1761–1765 (1978).CrossRefGoogle Scholar
  347. 347.
    T. Shiba, H. Uratani, I. Kubota, and Y. Sumi, Biopolymers 20, 1985–1987 (1981).CrossRefGoogle Scholar
  348. 348.
    L. P. Taylor, R. A. Hudson, and M. S. Dorscher, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 241–244, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar
  349. 349.
    I. H. Goldberg, M. Rabinowitz, and E. Reich, Proc. Natl. Acad. Sci. U.S.A. 48, 2094–2101 (1962).CrossRefGoogle Scholar
  350. 350.
    T. Takita, Y. Umezawa, S. Saito, H. Morishima, H. Umezawa, Y. Muraoka, M. Suzuki, M. Otsuka, S. Kobayashi, M. Ohno, T. Tsuchiya, T. Miyake, and S. Umezawa, in: Peptides: Synthesis, Structure and Function; Proceedings of the Seventh American Peptide Symposium (D. H. Rich and E. Gross, eds.), pp. 29–39, Pierce Chemical Co., Rockford, Ill. (1981).Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • James Samanen
    • 1
  1. 1.Peptide Chemistry DepartmentSmithkline Beckman, Inc.Palo AltoUSA

Personalised recommendations