Disulfide-bond formation plays an important role in the stabilization of the native conformation of peptides and proteins. In the case of multidisulfide-containing peptides and proteins, numerous folding intermediates are produced, including molecules that contain non-native and native disulfide bonds during in vitro folding. These intermediates can frequently be trapped covalently during folding and subsequently analyzed. The structural characterization of these kinetically trapped disulfide intermediates provides a clue to understanding the oxidative folding pathway. To investigate the folding of disulfide-containing peptides and proteins, in this unit, chemical methods are described for regulating regioselective disulfide formation (1) by using a combination of several types of thiol protecting groups, (2) by incorporating unique SeCys residues into a protein or peptide molecule, and (3) by combining with post-translational modification.
- Native chemical ligation
- Topological isomer