Isoaspartic acid (isoaspartate) is an amino acid that is an isomer of aspartic acid. It is formed via a chemical reaction in which the nitrogen atom of the following peptide group (in black at top right of Figure 1) nucleophilically attacks the γ-carbon of the side chain of an asparagine or aspartic acid residue, forming a symmetric succinimide intermediate (in red). Hydrolysis of the intermediate results in two products, either aspartic acid (in black at left) or isoaspartic acid, which is a β-amino acid (in green at bottom right). The reaction also results in the deamidation of the asparagine residue. Racemization may occur leading to the formation of D-aminoacids.
Kinetics of isoaspartyl formation
Isoaspartyl formation proceeds much more quickly if the asparagine is followed by a small, flexible residue (such as Gly) that leaves the peptide group open for attack. These reactions also proceed much more quickly at elevated pH (>10) and temperatures.
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