Peptide N-Terminal Modification

Although many of the most widely recognized post-translational modifications are characteristic of secretory or cell-surface proteins, most proteins, whatever their ultimate cellular desination, undergo some modification. For proteins synthesized completely within the cytoplasm, the earliest and most widespread are removal or modification of the N-terminal residue. In many proteins the N-terminal α-ammonium group (PK=8) undergoes secondary modification.

N-terminal modification reduces overall solubility of the peptide by reducing its overall charges. However, the stability of the peptide could also be increased because N terminal modification generates a closer mimic of the native protein. Therefore, these modifications might increase the biological activity of a peptide and prevent degradation by enzymes.