Amino Acids

, Volume 44, Issue 5, pp 1357–1363

Side reactions in the SPPS of Cys-containing peptides

  • Panagiotis Stathopoulos
  • Serafim Papas
  • Charalambos Pappas
  • Vassilios Mousis
  • Nisar Sayyad
  • Vassiliki Theodorou
  • Andreas G. Tzakos
  • Vassilios Tsikaris
Original Article

Abstract

Alkylation of sensitive amino acids during synthesis of biologically important peptides is a common and well-documented problem in Fmoc-based strategy. Herein, we probed for the first time an unexpected S-alkylation of Cys-containing peptides that occur during the final TFA cleavage of peptides from the Wang solid support. Through a battery of approaches (NMR, UV and LC–MS) the formed by-product was assigned as the alkylation of the cysteine sulfydryl group by the p-hydroxyl benzyl group derived from the acidic Wang linker decomposition. Factors affecting this side reaction were monitored and a protocol that minimizes the presence of the by-product is reported.

Keywords

Solid phase peptide synthesis Wang resin decomposition Cysteine S-alkylation TFA cleavage 

Supplementary material

726_2013_1471_MOESM1_ESM.pdf (1.2 mb)
Supplementary material 1 (PDF 1251 kb)

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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Panagiotis Stathopoulos
    • 1
  • Serafim Papas
    • 1
  • Charalambos Pappas
    • 1
  • Vassilios Mousis
    • 1
  • Nisar Sayyad
    • 1
  • Vassiliki Theodorou
    • 1
  • Andreas G. Tzakos
    • 1
  • Vassilios Tsikaris
    • 1
  1. 1.Department of Chemistry, Section of Organic Chemistry and BiochemistryUniversity of IoanninaIoaninaGreece

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