Letters in Peptide Science

, Volume 4, Issue 2, pp 95–100 | Cite as

Engineering of zinc finger and MHC motifs to locked-in tertiary folds

  • Marc Mathieu
  • Christian Lehmann
  • Alain Razaname
  • Gabriele Tuchscherer
Article

Summary

The assembly of helical and β-sheet peptide blocks containing reactive chain ends results in highly branched chain architectures (‘locked-in folds’) mimicking native tertiary structures. This molecular kit strategy allows to bypass the protein folding problem in protein de novo design and gives access to protein mimetics of high thermodynamic stability. The validity of this concept is exemplified for the design and synthesis of locked-in folds mimicking the zinc finger and MHC folding motifs.

Keywords

Protein design Locked-in folds Chemoselective ligation Zinc finger motif MHC motif Protein mimetics Non-native architectures 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1a.
    Richardson, J.S., and Richardson, D.C., Trends Biochem. Sci., 14 (1989) 304.PubMedCrossRefGoogle Scholar
  2. 1b.
    Bryson, J.W., Betz, S.F., Lu, H.S., Suich, D.J., Zhou, H.X., O'Neil, K.T. and DeGrado, W.F., Science, 270 (1995), 935.PubMedGoogle Scholar
  3. 1c.
    Vuilleumier, S. and Mutter, M., Angew. Chem. Int. Ed. Engl., 28 (1989) 535.CrossRefGoogle Scholar
  4. 1d.
    Olofsson, S. and Baltzer, L., Folding Des., 1 (1996) 347.CrossRefGoogle Scholar
  5. 1e.
    Broo, K., Brive, L., Lundh, A.-C., Ahlberg, P. and Baltzer, L., J. Am. Chem. Soc., 118 (1996) 8172.CrossRefGoogle Scholar
  6. 1f.
    Struthers, M.D., Cheng, R.P. and Imperiali, B., Science, 271 (1996) 342.PubMedGoogle Scholar
  7. 2a.
    Creighton, T.E., Proteins, Freeman, New York, NY, U.S.A., 1984.Google Scholar
  8. 2b.
    Borman, S., Chem. Eng. News, 74 (1996) 29.Google Scholar
  9. 3.
    Mutter, M. and Tuchscherer, G., Makromol. Chem. Rapid Commun., 9 (1988) 437.CrossRefGoogle Scholar
  10. 4.
    Mutter, M., Tuchscherer, G., Miller, C., Altmann, K.H., Carey, R.I., Wyss, D.F., Labhardt, A.M. and Rivier, J.E., J. Am. Chem. Soc., 114 (1992) 1463.CrossRefGoogle Scholar
  11. 5.
    Dumy, P., Eggleston, I.M., Cervigni, S.E., Sila, U. Sun, X. and Mutter, M., Tetrahedron Lett., 36 (1995) 1255.CrossRefGoogle Scholar
  12. 6.
    Dumy, P., Eggleston, I.M., Esposito, G., Nicula, S. and Mutter, M., Biopolymers, 39 (1996) 297.PubMedCrossRefGoogle Scholar
  13. 7.
    Mutter, M. and Tuchscherer, G., In Symposium in Print, Highlights in Bioorganic Chemistry, Pure Appl. Chem., 68 (1996) 2153.Google Scholar
  14. 8.
    Tuchscherer, G. and Mutter, M., J. Pept. Sci. 1 (1995) 3.PubMedCrossRefGoogle Scholar
  15. 9.
    Mutter, M., Dumy, P., Garrouste, P., Lehmann, C., Mathieu, M., Peggion, C., Peluso, S., Razaname, A. and Tuchscherer, G., Angew. Chem., Int. Ed. Engl., 35 (1996) 1482.CrossRefGoogle Scholar
  16. 10a.
    Choo, Y. and Klug, A., Proc. Natl. Acad. Sci. USA, 91 (1994) 11163.PubMedCrossRefGoogle Scholar
  17. 10b.
    Jamieson, A.C., Wang, H. and Kim, S.-H., Proc. Natl. Acad. Sci. USA, 93 (1996) 12834.PubMedCrossRefGoogle Scholar
  18. 10c.
    Frankel, A.D., Berg, J.M. and Pabo, C.O., Proc. Natl. Acad. Sci. USA, 84 (1987) 4841.PubMedCrossRefGoogle Scholar
  19. 10d.
    Michael, S.F., Kilfoil, V.J., Schmidt, M.H., Amann, B.T. and Berg, J.M., Proc. Natl. Acad. Sci. USA, 89 (1992) 4796.PubMedCrossRefGoogle Scholar
  20. 10e.
    Desjarlais, J.R. and Berg, J.M., Proc. Natl. Acad. Sci. USA, 90 (1993) 2256.PubMedCrossRefGoogle Scholar
  21. 10f.
    Rebar, E. and Pabo, C.O., Science, 263 (1994) 671.PubMedGoogle Scholar
  22. 11.
    Pavletich, N.P. and Pabo, C.O., Science, 252 (1991) 809.PubMedGoogle Scholar
  23. 12.
    Rose, K., J. Am. Chem. Soc., 116 (1994) 30.CrossRefGoogle Scholar
  24. 13a.
    Liu, C.F. and Tam, J.P., Proc. Natl. Acad. Sci. USA, 91 (1994) 6584.PubMedCrossRefGoogle Scholar
  25. 13b.
    Dawson, P.E. and Kent, S.B.H., J. Am. Chem. Soc., 115 (1993) 7263.CrossRefGoogle Scholar
  26. 14.
    Tuchscherer, G., Tetrahedron Lett, 34 (1993) 8419.CrossRefGoogle Scholar
  27. 15.
    Mutter, M., Lehmann, C., Mathieu, M., Rohwedder, B. and Tuchscherer, G., Proc. Natl. Acad. Sci. USA, manuscript submitted.Google Scholar
  28. 16.
    Stewart, J.M. and Young, J.D., Solid Phase Peptide Synthesis, Pierce Chemical Co., Rockford, IL., U.S.A., 1984.Google Scholar
  29. 17.
    Wöhr, T., Wahl, F., Nefzi, A., Rohwedder, B., Sato, T., Sun, X. and Mutter, M., J. Am. Chem. Soc., 118 (1996) 9218.CrossRefGoogle Scholar
  30. 18.
    Stern, L.J., Brown, J.H., Jardetzky, T.S., Gorga, J.C., Urban, R.G., Strominger, J.L. and Wiley, D.C., Nature, 368 (1994) 215.PubMedCrossRefGoogle Scholar

Copyright information

© ESCOM Science Publishers B.V 1997

Authors and Affiliations

  • Marc Mathieu
    • 1
  • Christian Lehmann
    • 1
  • Alain Razaname
    • 1
  • Gabriele Tuchscherer
    • 1
  1. 1.Institute of Organic ChemistryUniversity of Lausanne, BCH-DorignyLausanneSwitzerland

Personalised recommendations