An Important Side Reaction Using the Thiol, 3,6-dioxa-1,8-octanedithiol (DODT), in 9-fluorenylmethoxycarbonyl-based Solid Phase Peptide Synthesis

J Pept Sci. 2014 Mar;20(3):186-90. doi: 10.1002/psc.2595. Epub 2013 Dec 18.

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.

Keywords: 3,6-dioxa-1,8-ocatanedithiol; alkylation; methionine; peptide cleavage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ethyl Ethers / chemistry*
  • Fluorenes / chemistry*
  • Mass Spectrometry
  • Solid-Phase Synthesis Techniques / methods*
  • Sulfhydryl Compounds / chemistry*

Substances

  • 3,6-dioxa-1,8-octanedithiol
  • 9-fluorenylmethoxycarbonyl
  • Ethyl Ethers
  • Fluorenes
  • Sulfhydryl Compounds