Chemical Protein Synthesis by Chemoselective #x03B1;-Ketoacid-Hydroxylamine (KAHA) Ligations with 5-Oxaproline.

Chemical protein synthesis enables the precise construction of proteins by employing solid-phase peptide synthesis and chemoselective ligations. One such chemoselective reaction suitable for protein synthesis is the α-Ketoacid-Hydroxylamine (KAHA) ligation. Fully unprotected peptides are ligated by a selective reaction between α-ketoacids and hydroxylamines to give native amide bonds. Herein, we describe the chemical synthesis of ubiquitin by a two-segment approach using the 5-oxaproline hydroxylamine.