Susceptibility of protein therapeutics to spontaneous chemical modifications by oxidation, cyclization, and elimination reactions.

Susceptibility of protein therapeutics to spontaneous chemical modifications by oxidation, cyclization, and elimination reactions.
Amino Acids. 2019 Oct 01;:
Authors: Grassi L, Cabrele C
Abstract
Peptides and proteins are preponderantly emerging in the drug market, as shown by the increasing number of biopharmaceutics already approved or under development. Biomolecules like recombinant monoclonal antibodies have high therapeutic efficacy and offer a valuable alternative to small-molecule drugs. However, due to their complex three-dimensional structure and the presence of many functional groups, the occurrence of spontaneous conformational and chemical changes is much higher for peptides and proteins than for small molecules. The characterization of biotherapeutics with modern and sophisticated analytical methods has revealed the presence of contaminants that mainly arise from oxidation- and elimination-prone amino-acid side chains. This review focuses on protein chemical modifications that may take place during storage due to (1) oxidation (methionine, cysteine, histidine, tyrosine, tryptophan, and phenylalanine), (2) intra- and inter-residue cyclization (aspartic and glutamic acid, asparagine, glutamine, N-terminal dipeptidyl motifs), and (3) β-elimination (serine, threonine, cysteine, cystine) reactions. It also includes some examples of the impact of such modifications on protein structure and function.
PMID: 31576455 [Pu...

Source: Amino Acids - September 30, 2019 Category: Biochemistry Authors: Grassi L, Cabrele C Tags: Amino Acids Source Type: research