An important side reaction using the thiol, 3,6-dioxa-1,8-octanedithiol (DODT), in 9-fluorenylmethoxycarbonyl-based solid phase peptide synthesis

Authors

  • Paul W. R. Harris,

    Corresponding author
    1. School of Chemical Sciences, The University of Auckland, Auckland, New Zealand
    2. Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
    • Correspondence to: Paul W. R. Harris, School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland 1142, New Zealand. E-mail: paul.harris@auckland.ac.nz

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  • Renata Kowalczyk,

    1. School of Chemical Sciences, The University of Auckland, Auckland, New Zealand
    2. Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
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  • Sung-Hyun Yang,

    1. School of Chemical Sciences, The University of Auckland, Auckland, New Zealand
    2. Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
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  • Geoffrey M. Williams,

    1. School of Chemical Sciences, The University of Auckland, Auckland, New Zealand
    2. Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
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  • Margaret A. Brimble

    1. School of Chemical Sciences, The University of Auckland, Auckland, New Zealand
    2. Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
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Abstract

A considerable quantity of an alkylation by-product is observed when using 3,6-dioxa-1,8-octanedithiol as a scavenger during acidic release of peptides containing the thioether amino acid methionine from the solid support. Adjustment of the cleavage conditions by replacement of 3,6-dioxa-1,8-octanedithiol with ethane dithiol or by using methionine sulfoxide as an alternative to methionine resulted in no such impurity. The by-product was detectable by liquid chromatography and mass spectrometry and characterised by NMR spectroscopy of an isolated model peptide. It could be effectively removed in a separate post cleavage step by treatment with dilute aqueous acid at 37 °C. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

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