Perspectives in the Design of Peptide Analogues in Biomedical Applications

  • Serge A. St-Pierre
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


In 1971, when the late Josef Rudinger wrote The Design of Peptide Hormone Analogs for the series Drug Design, edited by E. J. Ariens (Rudinger, 1971), he was the pioneer in a discipline that has become a major trend in biomedical research: the design of drugs based on biologically active peptides.


Cyclic Peptide Peptide Design Peptide Drug Muramyl Dipeptide Conformational Restriction 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Banks, W. A., Kastin, A. J., and Coy, D. H., 1984, Evidence that [125I]N-Tyr-delta sleep-inducing peptide crosses the blood-brain barrier by a noncompetitive mechanism, Brain Res. 301:201–207.PubMedCrossRefGoogle Scholar
  2. Bhatnagar, P. K., Papas, E., Blum, H. E., Milich, D. R., Nitecki, D., Karels, M. J., and Vyas, G. N., 1982, Immune response to synthetic peptide analogues of hepatitis B surface antigen for the a determinant, Proc. Natl. Acad. Sci. U.S.A. 79:4400–4404.PubMedCrossRefGoogle Scholar
  3. Biddle, J. L., Houghten, R. A., Alexander, H., Shinnick, T. M., Sutcliff, J. G., Lerner, R. A., Rowlands, D. J., and Brown, F., 1982, Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence, Nature 298:30–33.CrossRefGoogle Scholar
  4. Blake, J., Ferrara, P., and Li, C. H., 1981, Beta-endorphin: Synthesis and radioligand binding activity of analogs containing cystine bridges, Int. J. Peptide Protein Res. 17:239–242.CrossRefGoogle Scholar
  5. Blanc, J. P., and Kaiser, E. T., 1984, Biological and physical properties of a beta-endorphin analog containing only D-amino acids in the amphiphilic helical segment 13-31, J. Biol. Chem. 259:9549–9556.PubMedGoogle Scholar
  6. Boer, G. J., van der Woude, T. P., Kruisbrink, J., and van Heerikhuize, J., 1984, Successful ventricular application of the miniaturized controlled-delivery Accurel technique for sustained enhancement of cerebrospinal fluid peptide levels in the rat, J. Neurosci. Methods 11:281–289.PubMedCrossRefGoogle Scholar
  7. Caranikas, S., Mizhari, J., D’Orléans-Juste, P., and Regoli, D., 1982, Antagonists of substance P, Eur. J. Pharmacol. 77:205–206.PubMedCrossRefGoogle Scholar
  8. Carelli, C., Audibert, F., Gaillard, J., and Chedid, L., 1982, Immunological castration of male mice by a totally synthetic vaccine administered in saline, Proc. Natl. Acad. Sci. U.S.A. 79:5392–5395.PubMedCrossRefGoogle Scholar
  9. Chipens, G. I., Mutulis, F. K., Batayev, B. S., Klusha, V. E., Misina, I. P., and Myshlyiakova, N. V., 1981, Cyclic analogs of bradykinin, Int. J. Peptide Protein Res. 18:302–311.CrossRefGoogle Scholar
  10. Chorev, M., Shavitz, R., Goodman, ML, Minick, S., and Guillemin, R., 1979, Partially modified retro-inverso enkephalinamides: Topochemical long-acting analogs in vitro and in vivo, Science 204:1210–1212.PubMedCrossRefGoogle Scholar
  11. DiMaio, J., Nguyen, T. M. D., Lemieux, C., and Schiller, P. W., 1982, Synthesis and pharmacological characterization in vitro of cyclic enkephalin analogues: Effect of conformational constraints on opiate receptor selectivity, J. Med. Chem. 25:1432–1438.PubMedCrossRefGoogle Scholar
  12. Djawari, D., Bolla, K., and Haneke, E., 1984, Treatment of recurrent herpes simplex with thymopoietin pentapeptide, Deut. Med. Wochenschr. 109:496–498.CrossRefGoogle Scholar
  13. du Vigneaud, V., Ressler, C., Swan, J. M., Roberts, C. W., Katsoyannis, P. G., and Gordon, S., 1953, The synthesis of oxytocin, J. Am. Chem. Soc. 75:4879–4885.CrossRefGoogle Scholar
  14. English, M. L., and Stammer, C. H., 1978, D-Ala2, dehydro-Phe4-Methionine enkephalinamide, a dehydropeptide hormone, Biochem. Biophys. Res. Commun. 85:780–782.PubMedCrossRefGoogle Scholar
  15. Fisher, G. H., Malborough, D. I., Ryan, J. W., Felix, A. M., 1978, L-3,4-Dihydroproline analogues of bradykinin: Synthesis, biological activity, and solution conformation, Arch. Biochem. Biophys. 189:81–85.PubMedCrossRefGoogle Scholar
  16. Freidinger, R. M., Veber, D. F., Perlow, D. S., Brooks, J. R., and Saperstein, R., 1980, Bioactive conformation of luteinizing hormone-releasing hormone: Evidence from a conformationally constrained analog, Science 210:656–658.PubMedCrossRefGoogle Scholar
  17. Fuxe, K., Agnati, L. F., Rosell, S., Harfstrand, A., Folkers, K., Lundberg, J. M., Andersson, K., and Hökfelt, T., 1982, Vasopressor effects of substance P and C-terminal sequences after intra-cisternal injection to alpha-chloralose-anesthetized rats: Blockade by a substance P antagonist, Eur. J. Pharmacol. 77:171–176.PubMedCrossRefGoogle Scholar
  18. Hrudy, V. J., and Mosberg, H. I., 1982, Structural, conformational, and dynamics considerations in the development of peptide hormone antagonists, in: Hormone Antagonists (M. K. Agarwal, ed.), W. DeGruder, New York, pp. 433–473.Google Scholar
  19. Iqbal, M., Balaram, P., Showell, H. J., Freer, R. J., and Becker, E. L., 1984, Conformationally constrained chemotactic peptide analogs of high biological activity, FEBS Lett. 165:171–174.PubMedCrossRefGoogle Scholar
  20. Jolicoeur, F. B., Barbeau, A., Rioux, F., Quirion, R., and St-Pierre, S., 1981, Differential neuro-behavioral effects of neurotensin and structural analogs, Peptides 2:171–176.PubMedCrossRefGoogle Scholar
  21. Key, M. E., Talmadge, J. E., Fogler, W. E., Bucano, C., and Fidler, I. J., 1982, Isolation of tumoricidal melanoma metastases of mice treated systemically with liposomes containing a lipophilic derivative of muramyl dipeptide, J. Natl. Cancer Inst. 69:1198.PubMedGoogle Scholar
  22. Labrie, F., Dupont, A., and Belanger, A., 1985, Complete androgen blockade for the treatment of prostrate cancer, in: Important advances in Onoclogy (V. T. De Vita, Jr., S. Hellman, and S. A. Rosenberg, eds.), J. B., Lippincott, Philadelphia, pp. 193–217.Google Scholar
  23. Marks, N., Stern, F., and Benuck, M., 1976, Correlation between biological potency and biodegradation of a somatostatin analogue. Nature 261:511–512.PubMedCrossRefGoogle Scholar
  24. Maton, P. N., O Dorisio, T. M., Howe, B. A., McArthur, K. E., Howard, J. M., Cherner, J. A., Malarkey, T. B., Collen, M. J., Gardner, J. D., and Jensen, R. T., 1985, Effect of a long-acting somatostatin analog (SMS 201-995) in a patient with pancreatic cholera, N. Engl. J. Med. 312:17–21.PubMedCrossRefGoogle Scholar
  25. Monahan, M. W., Amoss, M. S., Anderson, H. A., and Vale, W., 1973, Synthetic analogs of the hypothalamic luteinizing hormone releasing factor with increased agonist or antagonist properties, Biochemistry 12:4616–4620.PubMedCrossRefGoogle Scholar
  26. Moody, T. W., Pert, C. B., Gazdar, A. F., Carney, D. N., and Minna, J. D., 1981, High levels of intracellular bombesin characterize human small-cell carcinoma, Science 214:1246–1248.PubMedCrossRefGoogle Scholar
  27. Mosberg, H. I., Hruby, V. J., and Meraldi, J. P., 1981, Conformational study of the potent peptide hormone antagonist [1-penicillamine, 2-leucine]-oxytocin in aqueous solution, Biochemistry 20:2822–2828.PubMedCrossRefGoogle Scholar
  28. Ondetti, M. A., Rubin, B., and Cushman, D. W., 1977, Design of specific inhibitors of angiotensin-converting enzyme: New class of orally active antihypertensive agents, Science 196:441–444.PubMedCrossRefGoogle Scholar
  29. Pallai, P., Struthers, S., and Goodman, M., 1983, Extended retro-inverso analogs of somatostatin, Biopolymers 22:2523–2538.PubMedCrossRefGoogle Scholar
  30. Patchett, A. A., Harris, E., Tristram, E. W., Wyvratt, M. J., Wu, M. T., Taub, D., Peterson, E. R., Ikeler, T. J., ten Broeke, J., Payne, L. G., Ondeyka, D. L., Thorsett, E. D., Greenlee, W. J., Lohr, N. S., Hoffsommer, R. D., Joshua, H., Ruyle, W. V., Rothrock, J. W., Aster, S. D., Maycock, A. L., Robinson, F. M., Hirschmann, R., Sweet, C. S., Ulm, E. H., Gross, D. M., Vassil, T. C., and Stone, CA., 1980, A new class of angiotensin-converting enzyme inhibitors, Nature 288:280–283.PubMedCrossRefGoogle Scholar
  31. Pert, C. B., Pert, A., Chang, J. K., and Fong, B. T. W., 1976, [D-Ala2]-Met-enkephalinamide: A potent, long-lasting synthetic pentapeptide analgesic, Science 194:330–332.PubMedCrossRefGoogle Scholar
  32. Quirion, R., Rioux, F., Regoli, D., and St.-Pierre, S., 1980, Selective blockade of neurotensin induced coronary vessel constriction in perfused rat hearts by a neurotensin analog, Eur. J. Pharmacol. 61:309–312.PubMedCrossRefGoogle Scholar
  33. Rudinger, J., 1971, The design of peptide analogs, in: Drug Design, Vol. II (J. Ariens, ed.), Academic Press, New York, pp. 319–419.Google Scholar
  34. Rupp, W. M., Barbosa, J. J., Blackshear, P. J., McCarthy, H. B., Rohde, T. D., Goldberg, F. J., Rublein, T. G., Dorman, F. D., and Buchwald, H., 1982, The use of an implantable insulin pump in the treatment of type II diabetes, N. Engl. J. Med. 307:265–270.PubMedCrossRefGoogle Scholar
  35. Sanders, L. M., 1984, An injectable biodegradable controlled release delivery system for LHRH analogues, in: Proceedings of the VII International Congress of Endocrinology (F. Labrie and L. Proulx, eds.), Excerpta Medica, Elsevier Science, Amsterdam, p. 1018.Google Scholar
  36. Sawyer, T. K., Hruby, V. J., Darman, P. S., and Hadley, M. E., 1982, [half-Cys4, half-Cyslo]-Alpha-melanocyte-stimulating hormone: A cyclic alpha-melanotropin exhibiting superagonist biological activity, Proc. Natl. Acad. Sci. U.S.A. 79:1751–1755.PubMedCrossRefGoogle Scholar
  37. Shapira, M., Jibson, M., Müller, G., and Arnon, R., 1984, Immunity and protection against influenza virus by synthetic peptide corresponding to antigenic sites of hemagglutinin, Proc. Natl. Acad. Sci. U.S.A. 81:2461–2465.PubMedCrossRefGoogle Scholar
  38. Veber, D. F., Saperstein, R., Nutt, R. F., Freidinger, R. M., Brady, S. F., Curley, P., Perlow, D. S., Palaveda, W. J., Colton, C. D., Zacchei, A. G., Tocco, D. J., Hoff, D. R., Vandlen, R. L., Gerich, J. E., Hall, L., Mandarino, K., Cordes, E. H., Anderson, P. S., and Hirschmann, R., 1984, A super active cyclic hexapeptide analog of somatostatin, Life Sci. 34:1371–1378.PubMedCrossRefGoogle Scholar
  39. Wolfsen, A., and Odell, W., 1982, Advances in the use of peptide hormones as tumor markers, in: Cancer Diagnosis: New Concepts and Techniques (R. J. Stechel and R. A. Kagan, eds.), Grune and Stratton, Orlando, Florida, pp. 63–79.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Serge A. St-Pierre
    • 1
  1. 1.INRS-SantéInstitut National de la Recherche ScientifiqueMontrealCanada

Personalised recommendations