Side-chain thioamides as fluorescence quenching probes

Biopolymers. 2021 Jan;112(1):e23384. doi: 10.1002/bip.23384. Epub 2020 Jun 17.

Abstract

Thioamides, single atom oxygen-to-sulfur substitutions of canonical amide bonds, can be valuable probes for protein folding and protease studies. Here, we investigate the fluorescence quenching properties of thioamides incorporated into the side-chains of amino acids. We synthesize and incorporate Fmoc-protected, solid-phase peptide synthesis building blocks for introducing Nε -thioacetyl-lysine and γ-thioasparagine. Using rigid model peptides, we demonstrate the distance-dependent fluorescence quenching of these thioamides. Furthermore, we describe attempts to incorporate of Nε -thioacetyl-lysine into proteins expressed in Escherichia coli using amber codon suppression.

Keywords: FRET; fluorescence; quenching; thioamide; unnatural amino acid.

MeSH terms

  • Amino Acids / chemistry
  • Fluorescence Resonance Energy Transfer
  • Fluorescent Dyes / chemistry*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Solid-Phase Synthesis Techniques
  • Thioamides / chemistry*

Substances

  • Amino Acids
  • Fluorescent Dyes
  • Peptides
  • Thioamides