deamidate

Deamidation is the chemical removal of an amide functional group from a molecule. In biology, it most often refers to the hydrolysis of side-chain amide groups in the amino acids asparagine and glutamine within peptides and proteins, yielding aspartic acid or glutamic acid, respectively, and releasing ammonia. Deamidation can also describe the broader removal of amide groups from other compounds, but in biochemistry it is frequently discussed as a post-translational modification affecting proteins.

Non-enzymatic deamidation of asparagine and glutamine occurs spontaneously under physiological or elevated temperatures and varying pH. For asparagine, deamidation proceeds through a succinimide intermediate and can yield either aspartate or isoaspartate; isoaspartate introduces a beta-linkage that can alter protein conformation. Glutamine deamidation forms glutamate. The rate of these reactions depends on sequence context, local structure, pH, temperature, and aging or storage conditions. In contrast, enzymatic deamidation is carried out by specialized enzymes, such as amidases or deamidases (for example asparaginase and glutaminase), which hydrolyze amide bonds to carboxylates and ammonia for metabolic or therapeutic purposes.

Biological and practical significance is substantial. Deamidation changes charge and hydrophilicity, potentially altering protein folding, stability, activity, and antigenicity. It is a common form of protein aging and can contribute to loss of function or aggregation. In therapeutic proteins, deamidation is a critical quality attribute that can affect efficacy and immunogenicity. Repair mechanisms, such as the activity of protein L-isoaspartyl methyltransferase on isoaspartate residues, help mitigate some effects of deamidation.

In research and industry, deamidation is analyzed in proteomics and biopharmaceutical development, and it is considered both a natural aging process and a possible artifact of sample preparation.