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Deamidation reaction of Asn-Gly (top right) to Asp-Gly (at left) or iso(Asp)-Gly (in green at bottom right).

Deamidation is a chemical reaction in which an amide functional group is removed from an organic compound. In biochemistry, the reaction is important in the degradation of proteins because it damages the amide-containing side chains of the amino acids asparagine and glutamine.

In the biochemical deamidation reaction, the side chain of an asparagine attacks the following peptide group (in black at top right of Figure), forming a symmetric succinimide intermediate (in red). The symmetry of the intermediate results in two products of its hydrolysis, either aspartate (in black at left) or in isoaspartate, which is a beta amino acid (in green at bottom right). This process is considered a deamidation because the amide in the asparagine side chain is replaced by a carboxylate group. However, a similar reaction can occur in aspartate side chains, yielding a partial conversion to isoaspartate.

Kinetics of deamidation

Deamidation reactions have been conjectured to be one of the factors that limit the useful lifetime of proteins.

Deamidation proceeds much more quickly if the susceptible amino acid is followed by a small, flexible residue such as glycine whose low steric hindrance leaves the peptide group open for attack. Deamidation reactions also proceed much more quickly at elevated pH (>10) and temperature.

References

Clarke S. (1987) "Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins", Int. J., Peptide Protein Res., 30, 808-821. PMID 3440704
Stephenson RC and Clarke S. (1989) "Succinimide Formation from Aspartyl and Asparaginyl Peptides as a Model for the Spontaneous Degradation of Proteins", J. Biol. Chem., 264, 6164-6170. PMID 2703484
Robinson NE, Robinson AB. Molecular Clocks: Deamidation of Asparaginyl and Glutaminyl Residues in Peptides and Proteins. Althouse Press: Cave Junction, Ore. OCLC 56978028

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English Journal

Application of protein N-terminal amidase in enzymatic synthesis of dipeptides containing acidic amino acids specifically at the N-terminus.

Arai T, Noguchi A, Takano E, Kino K.SourceDepartment of Applied Chemistry, Faculty of Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku-ku, Tokyo 169-8555, Japan.
Journal of bioscience and bioengineering.J Biosci Bioeng.2013 Apr;115(4):382-7. doi: 10.1016/j.jbiosc.2012.10.024. Epub 2012 Dec 4.
Dipeptides exhibit unique physiological functions and physical properties, e.g., l-aspartyl-l-phenylalanine-methyl ester (Asp-Phe-OMe, aspartame) as an artificial sweetener, and functional studies of peptides have been carried out in various fields. Therefore, to establish a manufacturing process fo
PMID 23218487

Monoclonal antibody heterogeneity analysis and deamidation monitoring with high-performance cation-exchange chromatofocusing using simple, two component buffer systems.

Kang X, Kutzko JP, Hayes ML, Frey DD.SourcePurification and Process Research, Genzyme, a Sanofi Company, One the Mountain Road, Framingham, MA 01701, USA. Electronic address: Xuezhen.Kang@genzyme.com.
Journal of chromatography. A.J Chromatogr A.2013 Mar 29;1283:89-97. doi: 10.1016/j.chroma.2013.01.101. Epub 2013 Jan 31.
The use of either a polyampholyte buffer or a simple buffer system for the high-performance cation-exchange chromatofocusing of monoclonal antibodies is demonstrated for the case where the pH gradient is produced entirely inside the column and with no external mixing of buffers. The simple buffer sy
PMID 23428023

The use of native gels for the concomitant determination of protein sequences and modifications by mass spectrometry with subsequent conformational and functional analysis of native proteins following electro-elution.

Chen WQ, Karnaukhova E, Lubec G.SourceDepartment of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090, Vienna, Austria, chenweiqiang@gmail.com.
Amino acids.Amino Acids.2013 Mar 20. [Epub ahead of print]
The protocol consists of running a native gel with in-gel digestion by proteases, subsequent mass spectrometrical determination of protein sequence and modifications, followed by electro-elution and conformational analysis using melting point and circular dichroism. Finally, the eluted protein is te
PMID 23512611

Japanese Journal

Identification and characterization of oxidation and deamidation sites in monoclonal rat/mouse hybrid antibodies

TIMM Vera,GRUBER Patrick,WASILIU Michael,LINDHOFER Horst,CHELIUS Dirk
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 878(9), 777-784, 2010-03-15
NAID 10028033757

Conformational Variation Revealed by the Crystal Structure of RNase U2A Complexed with Ca Ion and 2'-Adenylic Acid at 1.03 Å Resolution

Noguchi Shuji
Protein & Peptide Letters 17(12), 1559-1561, 2010
… The structuresuggests that in solution the region around Asn32–Gly33 is likely to be in equilibrium between multiple conformers,with the deamidation of Asn32 proceeding when the region adopts an extended conformation. …
NAID 120002696073