Elsevier

Tetrahedron Letters

Volume 37, Issue 8, 19 February 1996, Pages 1187-1190
Tetrahedron Letters

Racemization studies of Fmoc-Cys(Trt)-OH during stepwise Fmoc-Solid phase peptide synthesis

https://doi.org/10.1016/0040-4039(95)02406-9Get rights and content

Abstract

In conventional stepwise Fmoc solid phase peptide synthesis, diisopropylethylamine (DIEA) base-catalyzed acylation methods lead to considerable amounts of racemization of Fmoc-Cys(Trt) residues during the activation/coupling process. The epimerization can be reduced to a negligible degree, via a base-free activation step.

During conventional stepwise Fmoc-based solid phase peptide synthesis, base-catalyzed acylation methods lead to considerable racemization of Cys(Trt)- assembled peptide fragments during the activation/coupling process. As demonstrated in this communication, the epimerization of Fmoc-Cys(Trt)-OH can be reduced to a negligible degree, applying an activation step in a neutral medium.

References (11)

  • P Lloyd-Williams et al.

    Tetrahedron

    (1993)
  • E Kaiser et al.

    Anal. Biochem.

    (1970)
  • H Frank et al.

    J. Chromatogr.

    (1978)
  • J Bernhagen et al.

    Biochemistry

    (1994)
  • T Kaiser et al.
There are more references available in the full text version of this article.

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