Chemical ligation from O-acyl isopeptides via 8- and 11-membered cyclic transition states

Unprotected O-acylated serine and O-acylated threonine isopeptides have been synthesized, and their conversion to native tripeptides and tetrapeptides by O- to N-terminus transfer investigated. Ligations involving 8- and 11-membered cyclic transition states are shown experimentally and computationally to be more favorable than intermolecular cross-ligations.