In-source fragmentation of peptide aldehydes and acetals: influence of peptide length and charge state

The use of in-source collision-induced dissociation (CID) was evaluated to generate structural information on peptide aldehydes, which represent an im portant class of compounds as inhibitors for serine and cysteine proteases and as key intermediates for protein engineering. By studying five peptide aldehydes of different lengths, and their peptide acetal counterparts, mass to charge (m/z) dependency of in-source fragmentation was established for peptides that differ only by their C-terminal functionalization. In-source fragmentation of peptide aldehydes and acetals leads to the same final ion, probably via a similar mechanism. Moreover, the gas-phase information obta ined here reflects the equilibrium occurring in solution between the peptid e aldehyde and its hydrated form, which was retained during the ionization process. The equilibrium constant was determined to be close to unity. Dist urbance of this equilibrium should enable the stability of covalent hydrati on of a given series of aldehydes to be compared. Copyright (C) 2001 John W iley & Sons, Ltd.