A Bottom-Up Approach To Preserve Thioamide Residue Stereochemistry during Fmoc Solid-Phase Peptide Synthesis

Org Lett. 2019 Sep 6;21(17):7015-7018. doi: 10.1021/acs.orglett.9b02598. Epub 2019 Aug 12.

Abstract

Thioamides are useful biophysical probes for the study of peptide structure and folding. The α-C stereochemistry of thioamide amino acids, however, is easily epimerized during solid-phase peptide synthesis (SPPS), which limits the sequence space that is available to thioamide incorporation. This work demonstrates that the α-C stereochemistry of thioamides can be reversibly protected in a manner that is compatible with the standard methodology of SPPS to enable the facile implementation of thioamide probes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Solid-Phase Synthesis Techniques*
  • Stereoisomerism
  • Thioamides / chemistry*

Substances

  • Peptides
  • Thioamides