MOLECULAR INSIGHTS THROUGH CHEMICAL PROBES: CUTTING-EDGE STRATEGIES FOR EXPLORING POSTTRANSLATIONAL MODIFICATIONS

Abstract

Chemical probes have become essential tools in the understanding of post-translational modifications (PTMs), which are the key factors in controlling the activity of proteins and the whole cell events. Besides, these alterations, e.g. phosphorylation, acetylation, and methylation, can greatly change the behavior of proteins and therefore are often associated with various health problems. PTMs were traditionally studied with methods like mass spectrometry and antibody-based techniques, which have a drawback of being not specific enough and not sensitive enough. The new methods have given rise to the invention of chemical probes which possess the ability to be highly selective and reactive towards certain PTMs. An example of such a tool is the use of covalent chemical reagents which apply chemical reactivity to mark the PTMs, thereby facilitating their detection and study. Furthermore, bioorthogonal probes allow the selective marking of PTMs in living cells which in turn enables monitoring of the protein modifications in real time. These probes have played a significant role in discovering PTMs that were previously unknown and also in gaining comprehension of the role of such PTMs in cell activity. The use of chemical probes is not limited to one area; they have found application in drug discovery soon where they help in specifying the potential targets for the treatment by clarifying the PTM map of the proteins. In addition, they play a role in the manufacture of diagnostic devices because they make it possible to detect diseaselinked PTMs. In short, chemical probes are radically changing our way of studying PTMs and providing us with new knowledge about protein function and the mechanisms of diseases.