Post-Translational Modification

Post-translational modifications (PTMs) are chemical changes to proteins occurring after their synthesis by ribosomes, fundamentally influencing protein structure, function, localisation, and interactions. These enzymatic alterations add functional diversity to the proteome far beyond what genetic sequences alone encode, playing crucial roles in cellular regulation and representing critical considerations in biopharmaceutical development.

Common PTMs include phosphorylation, glycosylation, acetylation, ubiquitination, and methylation, each serving distinct biological functions. Phosphorylation typically regulates enzyme activity and signal transduction, while glycosylation affects protein stability, immunogenicity, and receptor binding. For biopharmaceutical manufacturers, controlling PTMs represents both a challenge and opportunity. Therapeutic proteins produced in mammalian cell expression systems undergo complex glycosylation significantly impacting efficacy and safety profiles. Regulatory authorities mandate comprehensive PTM characterisation for biologics, including detailed glycan profiling. Biosimilar developers must demonstrate comparable PTM profiles to reference products, requiring sophisticated analytical techniques including mass spectrometry and chromatography. Companies invest heavily in expression system optimisation and process controls ensuring consistent, appropriate PTMs critical for therapeutic performance.