Traceless Preparation of C‐Terminal α‐Ketoacids for Chemical Protein Synthesis by α‐Ketoacid–Hydroxylamine Ligation: Synthesis of SUMO2/3

A novel protecting group for enantiopure α-ketoacids delivers C-terminal peptide α-ketoacids directly upon resin cleavage and allows the inclusion of all canonical amino acids, including cysteine and methionine. By using this approach, SUMO2 and SUMO3 proteins were prepared by KAHA ligation with 5-oxaproline. The synthetic proteins containing homoserine residues were recognized by and conjugated to RanGAP1 by SUMOylation enzymes.