KAHA Ligation

The α-Ketoacid-Hydroxylamine (KAHA) Amide-Forming Ligation is a chemical reaction that is used to join two unprotected fragments in peptide synthesis.

KAHA Ligation was developed by Jeffrey W. Bode group at ETH Zürich (previously University of Pennsylvania).

C-terminal ketoacid monomers are pre-loaded on resin via a linker for Fmoc-SPPS (Fmoc-based solid phase peptide synthesis).

Initial research utilised sulfur ylide linkers, but more recently the group developed acid- and photo-labile ketoacid monomers that can be loaded directly on Rink Amide resin.

The most commonly used N-terminal hydroxylamine is the 5-oxaproline, which results in a homoserine residue after ligation and O-N rearrangement.