Solid Phase Peptide Synthesis

  • Miklos Bodanszky

Abstract

By the conventional methods of organic synthesis the preparation of peptides containing more than just a few amino acids is an arduous task. Introduction of blocking groups, coupling reactions and deprotection steps entail a large number of operations such as washing the reaction mixtures neutral after coupling, precipitation or crystallization of intermediates, collecting solid products by filtration or centrifugation followed by drying etc. Thus, synthesis of peptide chains containing dozens of residues requires an almost heroic effort and proteins, even small ones, can be made by tour de force but certainly not routinely. The need for facilitation of the process was obvious for some time. The stepwise strategy, demonstrated in a novel synthesis of oxytocin (Bodanszky and du Vigneaud 1959) was, because of the repetitiveness of the operations conducive to experimentation with techniques suitable for mechanization and automation of chain building. Attachment of the (N-blocked) C-terminal residue to an insoluble polymeric support (a “resin”) followed by deprotection and acylation of the exposed amino group with the penultimate residue and continuation of the procedure by similar cycles of deprotection and incorporation absolve the practitioner from handling filters and separatory funnels, from washing and drying intermediates etc. Excess starting material and reagents as well as byproducts of the reactions are eliminated simply by washing the peptidyl polymer with appropriately selected solvents.

Keywords

Dichloromethane Transesterification Hydroxymethyl Hydrazide Carbodiimides 

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References

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Additional Sources

  1. Barany, G., Merrifield, R. B.: Solid Phase Peptide Synthesis, in The Peptides Vol. 2, Gross, E., Meienhofer, J., eds. pp. 1–284, Academic Press, New York 1980Google Scholar
  2. Birr, C.: Aspects of the Merrifield Peptide Synthesis, Springer Verlag, Berlin 1978CrossRefGoogle Scholar
  3. Stewart, J. M., Young, J. D.: Solid Phase Peptide Synthesis, 2nd ed., Pierce Chemical Co., Rockford, Illinois 1984Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • Miklos Bodanszky
    • 1
  1. 1.PrincetonUSA

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