Synthesis of Phosphopeptides in the Fmoc Mode

  • Troy J. Attard
  • Neil O’Brien-Simpson
  • Eric C. ReynoldsEmail author
Special Issue: Peptides in Oral and Dental Research


The synthesis of phosphopeptides has played a major role in the characterization of protein phosphorylation/dephosphorylation. The current range of synthesis protocols available provides a variety of possible routes by which to approach specific synthetic challenges, and this review article discusses these methods for the preparation of phosphopeptides and provides synthesis notes for each method. Phosphopeptide synthesis is achieved by either introduction of the phosphate group via post-synthetic (‘global’) phosphorylation of a resin-bound peptide or the incorporation of a pre-phosphorylated derivative into the growing peptide chain. Protocols and synthesis notes are provided for the synthesis of phosphoramidites, phosphotyrosyl, -seryl and -threonyl peptides and their mimetics, including thiophosphopeptides. The aim of this review was to provide a synthesis reference guide for Fmoc-based synthesis of both singly and multiply phosphorylated peptides, with particular emphasis given to the most successful and generally applicable methods.


Phosphopeptide Phosphoramidite Global phosphorylation H-phosphonate Dialkyl phosphate Monobenzyl phosphate Difluoromethyl phosphonate Thiophosphopeptide 



This work was supported by the National Health and Medical Research Council grant 251707 and The CRC for Oral Health Science.


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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Troy J. Attard
    • 1
  • Neil O’Brien-Simpson
    • 1
  • Eric C. Reynolds
    • 1
    Email author
  1. 1.Cooperative Research Centre for Oral Health Science, School of Dental Science, Bio21 Institute of Molecular Science and BiotechnologyThe University of MelbourneVICAustralia

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