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Letters in Peptide Science

, Volume 7, Issue 4, pp 207–215 | Cite as

Optimization of butanediol dimethacrylate crosslinked polystyrene: A novel polymeric support for solid phase peptide synthesis

  • P. K. Ajikumar
  • K. S. Devaky
Article

Summary

Studies leading to optimization of butanediol dimethacrylate-crosslinked polystyrene supports (BDDMA-PS) for solid phase peptide synthesis are delineated. BDDMA-PS copolymers with different crosslink densities were prepared and functionalised with chloromethyl groups. The reactivity of the Lys(2-Cl−Z)−OH residue bound to these polymers through a benzyl ester linkage was investigated by following the kinetics of acylation by the HOBt active ester of Boc-Alanine. From the results it was observed that the rate of peptide bond formation was maximum for a 2% BDDMA crosslinked resin. This resin was compared with a 2% DVB-crosslinked polystyrene resin (DVB-PS). Synthesis of an extremely insoluble, hydrophobic, antiparallel β-sheeted difficult sequence peptide LMVGGVVIA (β 34–42), C-terminal fragment of β-amyloid protein, β (1–42), was carried out on both 2% DVB-PS and 2% BDDMA-crosslinked polystyrene supports. The synthesis of the peptide was carried out using Boc amino acid strategy. Greater extent of swelling of the resino peptide, increased coupling efficiency during the assembly of amino acids and relatively high purity of synthesised peptide were observed in the case of 2% BDDMA-PS polymer.

Key words

butanediol dimethacrylate crosslinked polystyrene solid phase peptide synthesis 

Abbreviations: Abbreviations used according to the IUPAC-IUB commission of Biochemical nomenclature in, Eur. J. Biochem., 138 (1984) 9; J. Biol. Chem. 264 (1989) 663

Boc

t-Butoxycarbonil

DCC

Dicyclohexylcarbodiimide

DCM

Dichloromethane

DCU

Dicyclohexylurea

DIEA

N,N-Diisopropylethylamine

DMF

Dimethylformamide

DMSO

Dimethyl sulfoxide

HOBt

1-Hydroxybenzotriazole

NMP

N-methylpyrrolidone

TFA

Trifluroacetic acid

THF

Tetrahydrofuran

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References

  1. 1.
    Merrifield, R.B., J. Am. Chem. Soc., 85 (1963) 2149.CrossRefGoogle Scholar
  2. 2.
    Fields, G.B., Methods of Enzymology, 289 (1997) 3.CrossRefGoogle Scholar
  3. 3.
    Kent, S.B.H., Ann. Rev. Biochem., 57 (1988) 957.PubMedCrossRefGoogle Scholar
  4. 4.
    Zalipsky, S., Chang, J.L., Albericio, F. and Barany, G., React. Polym., 22 (1994) 243.CrossRefGoogle Scholar
  5. 5.
    Arshady, R., Artherton, E., Clive, D.L.J. and Sheppard, R.C., J. Chem. Soc., Perkin Trans. 1, (1981) 529.CrossRefGoogle Scholar
  6. 6.
    Meldal, M., Tetrahedron Lett., 33 (1992) 3077.CrossRefGoogle Scholar
  7. 7.
    Kempe, M. and Barany, G., J. Am. Chem. Soc., 118 (1996) 7083.CrossRefGoogle Scholar
  8. 8.
    Chandy, M.C. and Pillai, V.N.R., J. Polym. Sci., Part A: Polym Chem., 33 (1995) 849.CrossRefGoogle Scholar
  9. 9.
    Chandy, M.C. and Pillai, V.N.R., Polymer, 36 (1995) 1083.CrossRefGoogle Scholar
  10. 10.
    Renil, M., Nagaraj, R. and Pillai, V.N.R., Tetrahedron, 50 (1994) 6681.CrossRefGoogle Scholar
  11. 11.
    Varkey, J.T. and Pillai, V.N.R., J. Peptide Res., 51 (1998) 49.CrossRefGoogle Scholar
  12. 12.
    Ajikumar, P.K. and Devaky, K.S., Int. J. Chem., Sect B: Org. Chem. Incl. Med. Chem., 38 (1999) 783.Google Scholar
  13. 13.
    Havelson, K., Fraser, P.E., Krischner, D.A. and Lansbury Jr., P.T., Biochemistry, 29 (1990) 2639.CrossRefGoogle Scholar
  14. 14.
    Schnabel, E., Liebigs Ann. Chem., 702 (1967) 188.Google Scholar
  15. 15.
    Marvel, C.S. and Porter, P.K., Org. Synth. Coll. Vol. I, John Wiley & Sons, New York, 1967, 377.Google Scholar
  16. 16.
    Vogel's Text Book of Quantitative Inorganic Analysis, 4th Ed., Longman Group Ltd, Essex, England, 1978, p. 342.Google Scholar
  17. 17.
    Gisin, B.F., Anal. Chim. Acta., 58 (1972) 248.PubMedCrossRefGoogle Scholar
  18. 18.
    Kaiser, E., Colescott, R.L., Bossinger, C.D. and Cook, P.I., Anal. Biochem., 34 (1970) 595.PubMedCrossRefGoogle Scholar
  19. 19.
    Sherington, D.C. and Hodge, P. (Eds.), In Polymer Supported Reactions in Organic Synthesis, John Wiley & Sons, New York, 1980, pp. 469–477.Google Scholar
  20. 20.
    Feinberg, R.S. and Merrifield, R.B., Tetrahedron, 30 (1974) 3209.CrossRefGoogle Scholar
  21. 21.
    Stewart, J.M. and Young J.D., Solid Phase Peptide Synthesis, Pierce Chemical Co, Illinois, 1984, p. 54.Google Scholar
  22. 22.
    Gisin, B.F., Helv. Chem. Acta., 56 (1973) 1476.CrossRefGoogle Scholar
  23. 23.
    Barany, G. and Merrifield, R.B., In Gross, E. and Meienhofer, J. (Eds), The Peptides, Academic press, New York, 1979, pp. 1–284.Google Scholar
  24. 24.
    Hendrix, J.C., Halverson, K.J., Jarrett, J.T. and Lansbury Jr., P.T., J. Org. Chem., 55 (1990) 4517.CrossRefGoogle Scholar
  25. 25.
    Arunan, C. and Pillai, V.N.R., Protein and Peptide Lett., 6 (1999) 391.Google Scholar
  26. 26.
    Arunan, C. and Pillai, V.N.R., Tetrahedron, 56 (2000) 3005.CrossRefGoogle Scholar
  27. 27.
    Lazo, N.D. and Dowing, D.T., J. Pept. Res., 53 (1999) 633.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  1. 1.School of Chemical SciencesMahatma Gandhi UniversityKottayamIndia

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