Cysteine Promoted C-Terminal Hydrazinolysis of Native Peptides and Proteins

摘要

In 1998, the Ramage group demonstrated that a C-terminal hydrazide of a synthetic peptide could, following diazotiza-tion to the corresponding acyl azide, be transformed into usefully functionalized peptides, including thioesters. A drawback was that certain amino acid residues needed to be protected, but Liu and co-workers more recently showed that peptide and protein hydrazides could be converted into thioesters for use in native chemical ligation (NCL) under optimized conditions without protecting groups. Protein C-terminal hydrazides are useful products in their own right and allow selective modification of the protein through the uniquely reactive C-terminus. Until recently, a protein C-terminal hydrazide had only been obtained by hydrazinolysis of intein fusion precursors. Consequently, it is desirable that complementary routes become available, particularly for proteins that are not anticipated to express as soluble and folded intein fusion proteins.