Asparagine Deamidation: The Hidden Reaction That Changes Peptides in Storage
Asparagine and aspartic acid residues can rearrange through a cyclic succinimide intermediate, producing isomers that are hard to separate. A classic 1987 study explains the chemistry.
Some changes to a peptide do not alter its mass much at all, which makes them easy to miss. Deamidation and isomerisation at asparagine (Asn) and aspartic acid (Asp) residues are prominent examples.
The succinimide route
In 1987 Geiger and Clarke published a detailed study in the Journal of Biological Chemistry, Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. They showed that these reactions proceed through a cyclic succinimide intermediate formed when the backbone nitrogen of the following residue attacks the side chain.
Products of the reaction
Opening of the succinimide ring can give either the normal aspartyl linkage or an isoaspartyl linkage, in which the peptide backbone runs through the side-chain carbon. The succinimide can also racemise, generating D-forms. Deamidation of Asn adds only about one mass unit, and Asp/isoAsp isomers have identical mass.
Sequence and conditions matter
The rate depends strongly on the neighbouring residue and on solution conditions such as pH and temperature, which is why some sequences are much more susceptible than others.
Laboratory implications
For peptides containing Asn or Asp, storage as a dry lyophilised solid and limited time in solution reduce the opportunity for these reactions. Detecting the products generally needs a chromatographic method able to separate isomers, since a mass-only identity check may not distinguish them.
Scientific references
Primary source: Geiger T, Clarke S. Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation. J Biol Chem. 1987;262:785–794. — Source published 1 January 1987
For laboratory research information only. Not medical advice; no product is intended for human or veterinary use.