The Significance of Post-Translational Modification in Pharmaceutical Industry
SummaryThe analysis of proteins and peptides and their post-translational modifications is particularly important for the study of diseases where multiple genes are known to be involved, such as heart disease, cancer, and diabetes.
- Author Company: Creative Peptides
- Author Name: Cathy Miller
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Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. Proteins are synthesized by ribosomes that translate mRNA into polypeptide chains and then undergo PTM to form the mature protein product. After the protein is compounded, 20 different amino acids participate in protein PTM, such as protein phosphorylation, protein acetylation, as well as protein methylation, which play a significant role in almost all biological processes. Therefore, the synthesis of post-translationally modified peptides matters a lot in peptide discovery and development projects as well.
PTMs affect many aspects of protein functions and can be categorized into three main categories depending on the type of modification. The first and second groups are those PTMs that include the addition of chemical and complex groups to the target residue respectively, including glycosylation, prenylation, myristoylation, and palmitoylation. The last group consists of PTMs that combine polypeptides with the target residue, such as ubiquitylation and SUMOylation.
PTMs are frequently found in proteins with critical structures/functions such as secretory proteins, membrane proteins, and histones. These modifications can change many aspects of protein behaviors and characteristics, including enzyme function, protein lifespan, protein-protein interactions, receptor activation, protein folding, etc. Therefore, these modifications are involved in various biological processes such as signal transduction, gene expression regulation, gene activation, DNA repair, and cell cycle control. At present, PTMs are also extensively used to develop a variety of post-translationally modified peptides, including phosphopeptides, and other PTM peptides for proteomics, epigenetics, and immunology.
Examples of PTMs for peptides include acetylation, phosphorylation, ubiquitination, and so on. Phosphorylation is one of the most common PTMs and its mechanism is associated with the activity of regulating enzymes. Acetylation is catalyzed via lysine acetyltransferase (KAT) and histone acetyltransferase (HAT) enzymes, which are of importance in biological processes like chromatin stability, protein-protein interaction according to the available evidence. Ubiquitylation is an important reversible PTM, catalyzed by an enzyme complex that contains ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin ligase (E3) enzymes. By these PTM techniques above, scientific communities can achieve cysteine modifications, methionine modifications, phosphorylated peptides, and further post-translational modifications in the peptide field.
Many studies exploring the consequences of protein post-translational modifications in cells have been released over the last years. For instance, post-translational modifications have been reported to modulate p53's transcriptional activity and their influence on target gene expression, in particular those involved in cell cycle arrest and apoptosis. Additionally, the increase of protein glycation levels in diabetics under hyperglycemic conditions, which could further affect the bioactivity of important metabolism by protein glycation in diabetics, shows that altered PTM among serum proteins could affect normal protein functions and related to the pathogenesis of a disease.
PTMs alter the physicochemical properties of the peptide by changing the electrostatic charge, hydrophilicity, and conformation, thereby modulating their ability to specifically bind to the protein of interest. And PTM can also regulate protein folding, target specific subcellular compartments, interact with ligands or other proteins. As a result, the analysis of proteins and peptides and their post-translational modifications is particularly important for the study of diseases where multiple genes are known to be involved, such as heart disease, cancer, and diabetes.