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 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 iso(Asp), which is a β-amino acid (in green at bottom right). The reaction is called "deamidation", because the sidechain amide group of Asn is lost in favor of a carboxylate group. However, aspartate can also undergo this reaction, partially converting to iso(Asp). The term Side chain can have different meanings depending on the context: In chemistry and biochemistry a side chain is a part of a molecule attached to a core structure. ...
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 asparagine is followed by a small, flexible residue (such as Gly) that leaves the peptide group open for attack. Deamidation reactions also proceed much more quickly at elevated pH (>10) and temperatures. Detailed kinetic studies have been carried out by an Italian group?
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.
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.
Deamidation of asparagine (Asn) residues in peptides and proteins is one of the major pathways of chemical degradation.
The relationship between the deamidation rate constants of the model peptides in the solid state and the hydrophobicity of the residues in the N-1 and N-2 positions is shown in Figure 4.
22. Bhatt NP, Patel K, Borchardt RT. Chemical pathways of peptide degradation, I: deamidation of adrenocorticotropic hormone. Pharm Res. 1990;7:593-599.
Deamidation is a chemical reaction in which an amide functional group is removed from an organic compound.
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.
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