Abstract
Although most of the attention on the stability of protein and peptide pharmaceuticals has focused on denaturation and aggregation, chemical degradation cannot be ignored. A large number of possible chemical reactions have been identified as leading to decomposition of polypeptides (Manning et al., 1989). However, a select few are of primary concern to pharmaceutical scientists. In particular, hydrolysis and oxidation reactions appear to be the most common source of chemical instability. Hydrolysis of peptides refers to the nucleophilic addition of water to either an amide linkage in the peptide backbone (in a process known as proteolysis) or to an amide side chain of either asparagine or glutamine (known as deamidation). Meanwhile, oxidation can occur at cysteine residues (to form disulfide linkages), at methionine (to form sulfoxides), or at heterocyclic aromatic side chains of tryptophan and histidine (to form N-oxides).
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Meyer, J.D., Ho, B., Manning, M.C. (2002). Effects of Conformation on the Chemical Stability of Pharmaceutically Relevant Polypeptides. In: Carpenter, J.F., Manning, M.C. (eds) Rational Design of Stable Protein Formulations. Pharmaceutical Biotechnology, vol 13. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0557-0_4
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