Synthesis of Cysteine-Rich Peptides by Native Chemical Ligation without Use of Exogenous Thiols

Native chemical ligation (NCL) performed without resorting to the use of thiol additives was demonstrated to be an efficient and effective procedure for synthesizing Cys-rich peptides. This method using tris­(2-carboxyethyl)­phosphine (TCEP) as a reducing agent facilitates the ligation reaction even at the Thr-Cys or Ile-Cys site and enables one-pot synthesis of Cys-rich peptides throughout NCL and oxidative folding

<i>N</i>‑Sulfanylethyl­aminooxy­butyramide (SEAoxy): A Crypto-Thioester Compatible with Fmoc Solid-Phase Peptide Synthesis

An <i>N</i>-sulfanylethyl­amino­oxy­butyramide (SEAoxy) has been developed as a novel thioester equivalent for native chemical ligation. SEAoxy peptide was straightforwardly synthesized by conventional Fmoc solid-phase peptide synthesis without a problem. Moreover, SEAoxy peptide could be directly applied to native chemical ligation owing to the intramolecular <i>N</i>-to-<i>S</i> acyl shift that releases the peptide-thioester <i>in situ</i>. This methodology was successfully applied to the synthesis of two bioactive peptides