Letters in Peptide Science

, Volume 6, Issue 2–3, pp 135–142 | Cite as

Heterobifunctionalized tetraethylene glycol: A spacer for surface attachment of viral peptide epitopes for ELISA and derivatization of membrane modifying peptides

  • Jürgen Mack
  • Stefan Kienle
  • Dietmar Leipert
  • Thomas Redemann
  • Wolfgang Kraas
  • Günther Jung


New hydrophilic linkers of the formula Fmoc-NHCH2CH2COO(CH2CH2O)4X (X=COCH2CH2COOH Fmoc-Ats (2), X=CONHCH2COOH Fmoc-Atg (4) and X=CONHCH2CH2COOH Fmoc-Ata (5) have been prepared by heterobifunctional modification of tetraethylene glycol as starting material. These linkers represent a useful tool for solid phase peptide synthesis according to Fmoc/tBu strategy. Two examples are presented to illustrate the applicability of these building blocks: (i) spacing between biotin and a peptide epitope of the hepatitis C virus and evaluation in a biotin-streptavidin ELISA, and (ii) coupling of the new linker to the N- and C-terminus of the peptide antibiotic alamethicin to show eventual influences on the peptide's α-helical conformation.

Key words

alamethicin circular dichroism ELISA hepatitis C spacer tetraethylene glycol 



2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)


bovine serum albumine










phosphate buffered saline


polyethylene glycol


reversed phase


solid phase peptide synthesis


O-(1-H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate


tetraethylene glycol






Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1a.
    Harris, J.M. (Ed.), Poly(Ethylene Glycol) Chemistry, New York, 1992.Google Scholar
  2. 1b.
    Zalipsky S., Bioconjugate Chem., 6 (1995) 150.CrossRefGoogle Scholar
  3. 2a.
    Mutter, M., Hagenmaier, H. and Bayer, E., Angew. Chem. Int. Ed. Engl., 12 (1971) 811.CrossRefGoogle Scholar
  4. 2b.
    Lu, Y.A. and Felix A.M., Pept. Res., 6 (1993) 140.PubMedGoogle Scholar
  5. 3.
    Gerhardt, H. and Mutter, M., Polym. Bullet., 18 (1987) 487.Google Scholar
  6. 4.
    Frisch, B., Boeckler, C. and Schuber, F., Bioconjugate Chem., 7 (1996) 180.CrossRefGoogle Scholar
  7. 5.
    Zalipsky, S., Mullah, N., Harding, J.A., Gittelman, J., Guo, L. and DeFrees, S.A., Bioconjugate Chem., 8 (1997) 111.CrossRefGoogle Scholar
  8. 6.
    Slama, J. and Rando, R.R., Carbohydr. Res., 88 (1981) 213.CrossRefGoogle Scholar
  9. 7a.
    Boumrah, D., Campbell, M.M., Fenner, S. and Kinsman, R.G., Tetrahedron, 53 (1997) 6977.CrossRefGoogle Scholar
  10. 7b.
    Rupert, H., Huber, E., Josel, H.P., Klein, C. and Zink, B., EP 0410 280 A1 (1990).Google Scholar
  11. 8.
    Kraas, W., Ihlenfeldt, H.G., Seidel, C., Wienhues, U., Schmitt, U. and Jung, G., in Maia, H.L.S. (Ed.), Peptides 1994, Proc. 23rd Eur. Pept. Symp., ESCOM, Leiden, 1995, p. 827.Google Scholar
  12. 9.
    Kraas, W., Dissertation, Universität Tübingen, 1997.Google Scholar
  13. 10.
    Tam, J.P., Proc. Natl. Acad. Sci. USA, 85 (1988) 5409.PubMedCrossRefGoogle Scholar
  14. 11.
    Mueller, P. and Rudin, D.O., Nature, 217 (1968) 713.PubMedCrossRefGoogle Scholar
  15. 12a.
    Boheim, G., J. Membrane Biol., 19 (1974) 277.CrossRefGoogle Scholar
  16. 12b.
    Vogel, H., Nilsson, L., Rigler, R., Voges, K.-P. and Jung, G., Proc. Natl. Acad. Sci. USA, 85 (1988) 5067.PubMedCrossRefGoogle Scholar
  17. 12c.
    Vogel, H., Nilsson, L., Rigler, R., Meder, S., Boheim, G., Beck, W., Kurth, H.-H. and Jung, G., Eur. J. Biochem., 212 (1993) 305.PubMedCrossRefGoogle Scholar
  18. 13.
    Wenschuh, H., Beyermann, M., Haber, H., Seydel, J.K., Krause, E., Bienert, M., Carpino, L.A., El-Faham, A. and Albericio, F., J. Org. Chem., 60 (1995) 405.CrossRefGoogle Scholar
  19. 14.
    Chen, Y.-H., Yang, J.T. and Chau, K.H., Biochemistry, 13 (1974) 3350.PubMedCrossRefGoogle Scholar
  20. 15.
    Larwood, D.J. and Stoka, F.C., J. Labelled Comp. Radiopharm., 21 (1984) 603.Google Scholar
  21. 16.
    Ihlenfeldt, H.-G., Dissertation, Universität Tübingen (1995).Google Scholar
  22. 17.
    Jung, G., Dubischar, N. and Leibfritz, D., Eur. J. Biochem., 54 (1975) 395.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Jürgen Mack
    • 1
  • Stefan Kienle
    • 1
  • Dietmar Leipert
    • 1
  • Thomas Redemann
    • 1
  • Wolfgang Kraas
    • 1
  • Günther Jung
    • 1
  1. 1.Department of Organic ChemistryUniversity of TübingenTübingenGermany

Personalised recommendations