The ornithine effect in peptide cation dissociation.

Area of Science:

• Mass spectrometry
• Analytical chemistry
• Biochemistry

Background:

• Peptide fragmentation analysis is crucial for protein identification and characterization.
• Specific amino acid residues can influence fragmentation patterns, aiding in structural elucidation.
• Arginine residues, upon deguanidination, can form ornithine, potentially altering peptide fragmentation.

Purpose of the Study:

• To investigate and characterize the facile cleavage C-terminal to ornithine residues in gas-phase peptides, termed the ornithine effect.
• To compare the fragmentation patterns of arginine-containing peptides with their ornithine analogues.
• To evaluate the selectivity and potential applications of the ornithine effect in polypeptide ion fragmentation.

Main Methods:

• Gas-phase fragmentation of synthetic peptides containing ornithine residues.
• Comparison of fragmentation patterns between arginine and ornithine analogues (e.g., angiotensin II and its ornithine analogue).
• Analysis of ion mobility and proposed reaction mechanisms involving lactam ring formation.

Main Results:

• Observed facile cleavage C-terminal to ornithine residues, producing characteristic b- and y-ions or water loss.
• Conversion of arginine to ornithine decreases gas-phase proton affinity, facilitating cleavage via neighboring group participation.
• The ornithine effect was found to be a more favorable fragmentation pathway than the aspartic acid or proline effects under specific conditions.

Conclusions:

• The ornithine effect provides a highly selective cleavage mechanism at ornithine residues in gas-phase peptides.
• This effect is driven by favorable six-membered lactam ring formation.
• Converting arginine to ornithine can be a strategic approach to induce selective cleavages in polypeptide ions, complementing existing methods.