Facile Generation of Strained Peptidyl Thiolactones from Hydrazides and Its Application in Assembling MUC-1 VNTR OIigomers

An efficient method for the activation of C-terminal 4-mecaptoproline-or penicillamine-containing peptide hydrazides in ligation re-actions is reported herein.The corresp on ding peptide hydrazides can be readily prepared using solid-phase peptide synthesis,and subsequently activated by acetylacet one(acac)without exoge nous thiol additives.Strained peptidyl thiolactones could be the possible reactive in termediates that drastically accelerate the reacti on rates at the sterically demandi ng proline and valine sites.This developed protocol allows for sequential peptide ligations in a one-pot manner,and expedites the assembly of mucin 1(MUC-1)variable number tandem repeat(VNTR)trimers in various glycosylated forms.