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Synthetic Small Thymic Peptides

An Immunoregulatory Concept
  • Christian Birr
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

In 1976 we had started to collect human thymic tissue for the isolation and structural elucidation of immunoregulatory proteins. Specialized in protein chemistry and peptide synthesis (Birr, 1978, 1980), however, we immediately initiated the total synthesis of thymosin α1 when the sequence of this polypeptide consisting of 28 amino acid residues was published in 1977 (Goldstein et al.). Our methodological know-how in the synthesis of polypeptides rich in trifunctional amino acids furnished the total synthesis in solution of thymosin α1 within 2 years (Birr and Stollenwerk, 1979) including one less successful trial for the synthesis of the polypeptide.

Keywords

Total Synthesis Mixed Lymphocyte Culture Performic Acid Immunoregulatory Property Thymic Peptide 
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.

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References

  1. Abiko, T., Onodera, I., and Sekino, H., 1979a, The effect of a synthetic thymosin-ai fragment on the inhibition of E-rosette formation by the serum of a patient with nephrotic syndrome, Chem. Pharm. Bull. 27:3171–3180.PubMedCrossRefGoogle Scholar
  2. Abiko, T., Kumikawa, M., and Sekino, H., 1979b, Synthesis and effects of two peptide fragments of thymopoietin II on E-rosette forming cells in the uremic state, Chem. Pharm. Bull. 27:2233–2242.PubMedCrossRefGoogle Scholar
  3. Abiko, T., Onodera, I., and Sekino, H., 1980a, Synthesis and immunological effects of thymosin-α1 and its fragments on inhibitory factor in minimal change nephrotic syndrome, Chem. Pharm. Bull. 28:3542–3550.PubMedCrossRefGoogle Scholar
  4. Abiko, T., Sekino, H., and Higuchi, H., 1980b, The effect of thymosin-ai fragments on T-lymphocyte transformation in the uremic state, Chem. Pharm. Bull. 28:3411–3418.PubMedCrossRefGoogle Scholar
  5. Abiko, T., Onodera, I., and Sekino, H., 1980c, The effect of thymopoietin II fragments and their analogs on E-rosette forming cells in the uremic state, Chem. Pharm. Bull. 28:2507–2513.PubMedCrossRefGoogle Scholar
  6. Baker, P. E., Gillis, S., and Smith, K. A., 1979, Monoclonal cytolytic T-cell lines, J. Exp. Med. 149:273–278.PubMedCrossRefGoogle Scholar
  7. Birr, C., 1972, Der αα-Dimethyl-3.5.-dimethoxybenzyloxycarbonyl (Ddz)-Rest, eine photo- und säurelabile Stickstoffschutzgruppe für die Peptidchemie, Liebigs Ann. Chem. 763:162–172.CrossRefGoogle Scholar
  8. Birr, C., 1978, Reactivity and structure concepts in organic chemistry, Aspects of the Merrifield Peptide Synthesis, Vol. 8, Springer Verlag, Berlin.Google Scholar
  9. Birr, C. (ed), 1980, Methods in Peptides and Protein Sequence Analysis, Elsevier/North-Holland, Amsterdam.Google Scholar
  10. Birr, C., 1983, unpublished investigations on Thymus Mulli, Pharm. Co., Dr. Kurt Mulli Nachf., Neuenburg, FRG.Google Scholar
  11. Birr, C., and Stollenwerk, U., 1979, Synthese von Thymosin-α1, einem Polypeptid des Thymus, Angew. Chem. 91:422–423;CrossRefGoogle Scholar
  12. Birr, C., and Stollenwerk, U., 1979, Synthese von Thymosin-α1, einem Polypeptid des Thymus, Angew. Chem. Int. Ed. Engl. 18:394–395.PubMedCrossRefGoogle Scholar
  13. Birr, C., Nassal, M., and Pipkorn, R., 1979, Preparative merits of the mixed anhydride (MA) method in the excess use of Ddz-amino acids in the peptide synthesis of biologically active new antamanide analogues, Int. J. Pept. Protein Res. 13:287–295.PubMedCrossRefGoogle Scholar
  14. Birr, C., Stollen werk, U., Brodner, O., and Manke, H.-G., 1979b, Alternative routes in the synthesis of thymosin-ai and some of its biological activities, in: Peptides: Structure-Biology-Function (E. Gross and J. Meienhofer, eds.), pp. 397–407, Pierce Chemical Co., Rockford, Ill.Google Scholar
  15. Birr, C., Stollenwerk, U., Werner, I., Manke, H.-G., and Brodner, O., 1981a, Synthesis and properties of immunostimulating peptides, in: Peptides 1980 (K. Brunfeldt, ed.), pp. 420–427, Scriptor, Copenhagen.Google Scholar
  16. Birr, C., Krueck, I., Stollenwerk, U., Ciardelli, T. L., and Brodner, O., 1981b, Synthesis and properties of immunostimulating peptides. III. Potentiated immunomodulation by varied sequences of thymosin-α1, in: Peptides: Synthesis-Structure-Function (D. Rich and E. Gross, eds.), pp. 545–548, Pierce Chemical Co., Rockford, Ill.Google Scholar
  17. Blanot, D., Martinez, J., Sasaki, A., Anger, G., Bricas, E., Dardenne, M., and Bach, J. F., 1979, Synthetic analogs of serum thymic factor and their biological activities, in: Peptides: Structure-Biology-Function (E. Gross and J. Meienhofer, eds.), pp. 551–554, Pierce Chemical Co., Rockford, Ill.Google Scholar
  18. Chou, P. Y., and Fasmann, G. D., 1978, Prediction of the secondary structure of proteins from their amino acid sequence, Adv. Enzymol. 47:45–115.PubMedGoogle Scholar
  19. Ciardelli, T. L., Krueck, I., Birr, C., and Brodner, O., 1981, Synthesis and properties of immunostimulating peptides. II, in: Peptides: Synthesis-Structure-Function (D. Rich and E. Gross eds.), pp. 541–544, Pierce Chemical Co., Rockford, Ill.Google Scholar
  20. Ciardelli, T. L., Incefy, G. S., and Birr, C., 1982, Activity of synthetic thymosin-α1 C-terminal peptides in the azathioprine E-rosette inhibition assay, Biochemistry 21:4233–4237.PubMedCrossRefGoogle Scholar
  21. Freire, M., Crivellaro, O., Isaacs, C., Moschera, J., and Horecker, B. L., 1978, Translation of mRNA from calf thymus in the wheat germ system: Evidence for a precursor of thymosin-ai, Proc. Natl. Acad. Sci. USA 75:6007–6011.PubMedCrossRefGoogle Scholar
  22. Freire, M., Hannappel, E., Rey, M., Freire, J. M., Kido, H., and Horecker, B. L., 1981, Purification of thymus mRNA coding for a 16,000-dalton polypeptide containing the thymosin-ai sequence, Proc. Natl. Acad. Sci. USA 78:192–195.PubMedCrossRefGoogle Scholar
  23. Goldstein, A. L., Low, T. L. K., McAdoo, M, McClure, J., Thurman, G. B., Rossio, J., Lai, C.- Y., Chang, D., Wang, S.-S., Harvey, C., Ramel, A. H., and Meienhofer, J., 1977, Thymosin-α1: Isolation and sequence analysis of an immunologically active thymic polypeptide, Proc. Natl. Acad. Sci. USA 74:725–729.PubMedCrossRefGoogle Scholar
  24. Goldstein, G., Scheid, M., Boyse, E. A., Schlesinger, D. H., and Van Wauwe, J., 1979, A synthetic pentapeptide with biological activity characteristic of the thymic hormone thymopoietin, Science 204:1309–1310.PubMedCrossRefGoogle Scholar
  25. Hannappel, E., Davoust, S., and Horecker, B. L., 1982, Isolation of peptides from calf thymus, Biochem. Biophys. Res. Commun. 104:266–271.PubMedCrossRefGoogle Scholar
  26. Hooper, J. A., McDaniel, M. C., Thurman, G. B., Cohen, G. H., Schulof, R. S., and Goldstein, A. L., 1975, Purification and properties of bovine thymosin, Ann. N.Y. Acad. Sci. 249:125–138.PubMedCrossRefGoogle Scholar
  27. Imaizumi, A., Gyotoku, S., Terada, S., and Kimoto, E., 1981, Structural requirement for the biological activity of serum thymic factor, FEBS Lett. 128:108–111.PubMedCrossRefGoogle Scholar
  28. König, W., and Geiger, R., 1970, Eine neue Methode zur Synthese von Peptiden: Aktivierung der Carboxylgruppe mit Dicyclohexylcarbodiimid unter Zusatz von 1-Hydroxy-benzotriazol, Chem. Ber. 103:788–795.PubMedCrossRefGoogle Scholar
  29. Krueck, I., 1984, Doctoral thesis, University of Heidelberg, FRG.Google Scholar
  30. Nash, L., Good, R. A., Hatzfield, A., Goldstein, G., and Incefy, G. S., 1981, In vitro differentiation of two surface markers for immature T cells by the synthetic pentapeptide thymopoietin, J. Immunol. 126:150–156.PubMedGoogle Scholar
  31. Vaisius, A. C., and Horgen, P. A., 1980, The effects of several divalent cations on the activation or inhibition of RNA polymerases II, Arch. Biochem. Biophys. 203:553–564.PubMedCrossRefGoogle Scholar
  32. Vaisius, A.C., and Wieland, T., 1982, Formation of a single phosphodiester bond by RNA polymerase B from calf thymus is not inhibited by a-amanitine, Biochemistry 21:3097–3101.PubMedCrossRefGoogle Scholar
  33. Verhagen, H., DeCock, W., DeCree, J., and Goldstein, G., 1980, Comparison of the in vitro effects of thymopoietin pentapeptide and levamisole on peripheral E-rosette forming cells, Thymus 1:195–202.Google Scholar
  34. von Boehmer, H., Hengartner, H., Nabholz, M., Leonhardt, W., Schreier, M. H., and Haas, W., 1979, Firm specificity of a continuously growing killer cell clone specific for H-Y antigen, Eur. J. Immunol. 9:592–594.CrossRefGoogle Scholar
  35. Wang, S.-S., Kulesha, J. D., and Winter, D. P., 1979, Synthesis of thymosin-α1, J. Am. Chem. Soc. 101:253–257.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Christian Birr
    • 1
  1. 1.Max-Planck-Institut für Medizinische Forschung, and OrganogenMedizinisch-Molekularbiologische Forschungsgesellschaft m.b.H.HeidelbergFederal Republic of Germany

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