Skip to main content
SpringerLink
Log in

1H nuclear magnetic resonance determination of the membrane-bound conformation of senktide, a highly selective neurokinin B agonist

  • Research Papers
  • Published:
Journal of Biomolecular NMR Aims and scope Submit manuscript

Summary

Senktide is a highly specific and potent analog of neurokinin B, the natural ligand of the tachykinin receptor NK-3. The membrane-bound conformation of senktide, interacting with negatively charged membrane vesicles composed of perdeuterated phosphatidylcholine and phosphatidylglycerol (70:30), has been investigated using two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY). The occurrence of an N-methylated phenylalanine in the peptide's sequence induces a cis-trans-isomerisation of the corresponding peptide bond which is slow on the chemical-shift scale. NMR data indicate a much stronger membrane affinity of the trans isomer, allowing the determination of a highly resolved membrane-bound conformation using distance geometry and energy minimization. The membrane-bound backbone conformation of several residues is found to be close to a left-handed helix, certainly due to the presence of nonnatural residues (succinylated N-terminal, N-methyl-phenylalanine) as well as a glycine. The results are discussed in the context of a possible biological relevance of the membrane-bound conformation, in terms of the affinity and specificity of this neuropeptide.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Banks, K.M., Hare, D.R. and Reid, B.R. (1989) Biochemistry, 28, 6996–7010.

    Google Scholar 

  • Bax, A. and Davis, D.G. (1985a) J. Magn. Reson., 63, 207–213.

    Google Scholar 

  • Bax, A. and Davis, D.G. (1985b) J. Magn. Reson., 65, 355–360.

    Google Scholar 

  • Behling, R.W. and Jelinski, L.W. (1990) Biochem. Pharmacol., 40, 49–54.

    Google Scholar 

  • Bersch, B., Stark, J.P., Milon, A., Nakatani, Y. and Ourisson, G. (1993) Bull. Soc. Chim. Fr., in press.

  • Billeter, M., Braun, W. and Wüthrich, K. (1982) J. Mol. Biol., 155, 321–346.

    Google Scholar 

  • Bothner-By, A.A., Stephens, R.L., Lee, J., Warren, C.D. and Jeanloz, R.W. (1984) J. Am. Chem. Soc., 106, 811–813.

    Google Scholar 

  • Braunschweiler, L., Bodenhausen, G. and Ernst, R.R. (1983) Mol. Phys., 48, 535–560.

    Google Scholar 

  • Braunschweiler, L. and Ernst, R.R. (1983) J. Magn. Reson. 53, 521–528.

    Google Scholar 

  • Buck, S.H., Van Giersbergen, P.L.M. and Burcher, E. (1991) Neurochem. Int., 18, 167–170.

    Google Scholar 

  • Campbell, A.P. and Sykes, B.D. (1991) J. Magn. Reson., 93, 77–92.

    Google Scholar 

  • Cascieri, M.A., Chicchi, G.G., Freidinger, R.M., Dylion Colton, C., Perlow, D.S., Williams, B., Curtis, N.R., McKnight, A.T., Maguire, J.J., Veber, D.F. and Liang, T. (1986) Mol. Pharmacol., 29, 34–38.

    Google Scholar 

  • Chassaing, G., Convert, O. and Lavielle, S. (1986) Eur. J. Biochem., 154, 77–85.

    Google Scholar 

  • Clore, G.M. and Gronenborn, A.M. (1983) J. Magn. Reson. 53, 423–442.

    Google Scholar 

  • Dam, T.V., Escher, E. and Quirion, R. (1990) Brain Res., 506, 175–179.

    Google Scholar 

  • Drapeau, G., D'Orléans-Juste, P., Dion, S., Rhaleb, N.E. and Regoli, D. (1987) Eur. J. Pharmacol., 136, 401–403.

    Google Scholar 

  • Gasteiger, J. and Marsili, M. (1980) Tetrahedron, 36, 3219–3228.

    Google Scholar 

  • Guard, S. and Watson, S.P. (1991) Neurochem. Int. 18, 149–165.

    Google Scholar 

  • Guard, S., Watson, S.P., Maggio, J.E., Too, H.P. and Watling, K.J. (1990) Brit. J. Pharmacol., 99, 767–773.

    Google Scholar 

  • Hruby, V.J. (1982) Life Sci., 31, 189–199.

    Google Scholar 

  • Iijima, H., Dunbar, J.B. and Marshall, G.R. (1987) Protein Struct. Funct. Genet., 2, 330–339.

    Google Scholar 

  • Jeener, J., Meier, B.H., Bachmann, P. and Ernst, R.R. (1979) J. Chem. Phys., 71, 4546–4553.

    Google Scholar 

  • Jelicks, L.A., Broido, M.S., Becker, J.M. and Naider, F.R. (1989) Biochemistry, 28, 4233–4240.

    Google Scholar 

  • Kingsley, P.B. and Feigenson, G.W. (1979) Chem. Phys. Lipids, 24, 135–147.

    Google Scholar 

  • Koehl, P., Lefèvre, J.F. and Jardetzky, O. (1992) J. Mol. Biol., 223, 299–315.

    Google Scholar 

  • Laufer, R., Gilon, C., Chorev, M. and Selinger, Z. (1986) J. Biol. Chem., 261, 10257–10263.

    Google Scholar 

  • Lavielle, S., Chassaing, G., Ploux, O., Loeuillet, D., Besseyre, J., Julien, S., Marquet, A., Convert, O., Beaujouan, J.C., Torrens, Y., Bergström, L., Saffroy, M. and Glowinski, J. (1988) Biochem. Pharmacol., 37, 41–49.

    Google Scholar 

  • Levian-Teitelbaum, D., Kolodny, N., Chorev, M., Selinger, Z. and Gilon, C. (1989) Biopolymers, 28, 51–64.

    Google Scholar 

  • Lippens, G.M., Cerf, C. and Hallenga, K. (1992) J. Magn. Reson. 99, 268–281.

    Google Scholar 

  • Loeuillet, D., Convert, O., Lavielle, S. and Chassaing, G. (1989) Int. J. Pept. Protein Res., 33, 171–180.

    Google Scholar 

  • London, R.E., Perlman, M.E. and Davis, D.G. (1992) J. Magn. Reson. 97, 79–98.

    Google Scholar 

  • Macura, S. and Ernst, R.R. (1980) Mol. Phys., 41, 95–117.

    Google Scholar 

  • Maggio, J.E. (1988) Annu. Rev. Neurosci. 11, 13–28.

    Google Scholar 

  • Manavalan, P. and Momany, F.A. (1980) Biopolymers, 19, 1943–1973.

    Google Scholar 

  • Mareci, T.H. and Freeman, R. (1983) J. Magn. Reson. 51, 531–535.

    Google Scholar 

  • Marion, D. and Wüthrich, K. (1983) Biochem. Biophys. Res. Commun., 113, 967–974.

    Google Scholar 

  • McLachlan, A.D. (1979) J. Mol. Biol., 128, 49–79.

    Google Scholar 

  • Milon, A., Miyazawa, T. and Higashijima, T. (1990) Biochemistry 29, 65–75.

    Google Scholar 

  • Nakanishi, S. (1991) Annu. Rev. Neurosci., 14, 123–136.

    Google Scholar 

  • Plateau, P. and Guéron, M. (1982) J. Am. Chem. Soc., 104, 7310–7311.

    Google Scholar 

  • Rance, M., Sørensen, O.W., Bodenhausen, G., Wagner, G., Ernst, R.R. and Wüthrich, K. (1983) Biochem. Biophys. Res. Commun., 117, 479–485.

    Google Scholar 

  • Regoli, D., Dion, S., Rhaleb, N.E., Rouissi, N., Tousignant, C., Jukic, D., D'Orleans-Juste, P. and Drapeau, G. (1989) Biopolymers, 28, 81–90.

    Google Scholar 

  • Regoli, D., Drapeau, G., Dion, S. and Couture, R. (1988) Trends Pharmacol. Sci. 9, 290–295.

    Google Scholar 

  • Sargent, D.F., Bean, J.W. and Schwyzer, R. (1988) Biophys. Chem., 31, 183–193.

    Google Scholar 

  • Sargent, D.F., Bean, J.W. and Schwyzer, R. (1989) biophys. Chem. 34 103–114.

    Google Scholar 

  • Sargent, D.F. and Schwyzer, R. (1986) Proc. Natl. Acad. Sci. USA 83, 5774–5778.

    Google Scholar 

  • Saulitis, J. and Liepins, E. (1990) J. Magn. Reson. 87, 80–91.

    Google Scholar 

  • Schwyzer, R. (1987) EMBO. J., 6, 2255–2259.

    Google Scholar 

  • Schwyzer, R. (1991) Biopolymers, 31, 785–792.

    Google Scholar 

  • Schwyzer, R., Erne, D. and Rolka, K. (1986) Helv. Chim. Acta, 69, 1789–1797.

    Google Scholar 

  • Seelig, A. and Macdonald, P.M. (1989) Biochemistry, 28, 2490–2496.

    Google Scholar 

  • Shaka, A.J. and Freeman, R. (1983) J. Magn. Reson., 51, 169–173.

    Google Scholar 

  • Sumner, S.C.J. and Ferretti, J.A. (1989) FEBS Lett., 253, 117–120.

    Google Scholar 

  • Wakamatsu, K., Okada, A., Suzuki, M., Higashijima, T., Masui, Y., Sakakibara, S. and Miyazawa, T. (1986) Eur. J. Biochem., 154, 607–615.

    Google Scholar 

  • Wakamatsu, K., Okada, A., Suzuki, M., Higashijima, T., Sakakibara, S. and Miyazawa, T. (1987) Eur. J. Biochem., 163, 331–338.

    Google Scholar 

  • Williamson, M.P. and Neuhaus, D. (1987) J. Magn. Reson. 72, 449–457.

    Google Scholar 

  • Wormser, U., Laufer, R., Hart, Y., Chorev, M., Gilon, C. and Selinger, Z. (1986) EMBO J., 5, 2805–2808.

    Google Scholar 

  • Wüthrich, K. (1986) NMR of Proteins and Nucleic Acids, Wiley, New York.

    Google Scholar 

  • Wüthrich, K., Billeter, M. and Braun, W. (1983) J. Mol. Biol., 169, 949–961.

    Google Scholar 

Download references

Author information

Author notes

  1. Beate Bersch

    Present address: Institut de Biologie Structurale, CNRS-CEA, 41 Avenue des Martyrs, 38027, Grenoble Cedex 1, France

Authors and Affiliations

  1. Laboratoire de Chimie Organique des Substances Naturelles, associé au CNRS, Centre de Neurochimie, Université Louis Pasteur, 5 rue Blaise Pascal, 67084, Strasbourg, France

    Beate Bersch, Yoichi Nakatani & Guy Ourisson

  2. IBMC du CNRS, 15 rue Descartes, 67084, Strasbourg Cedex, France

    Patrice Koehl

  3. Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS, Université Paul Sabatier, 118 route de Narbonne, 31062, Toulouse, France

    Alain Milon

Authors
  1. Beate Bersch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrice Koehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoichi Nakatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guy Ourisson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alain Milon
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bersch, B., Koehl, P., Nakatani, Y. et al. 1H nuclear magnetic resonance determination of the membrane-bound conformation of senktide, a highly selective neurokinin B agonist. J Biomol NMR 3, 443–461 (1993). https://doi.org/10.1007/BF00176010

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00176010

Keywords

Search

Navigation