The Search for Covalently Ligandable Proteins in Biological Systems

Abstract

This commentary highlights the recent article published in Nature, June 2016, titled: “Proteome-wide covalent ligand discovery in native biological systems”. They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here.

Keywords

• fragment-based ligand discovery
• covalent binding ligands
• druggable cysteines
• isotopic tandem orthogonal proteolysis‒activity-based protein profiling
• methyl transferase
• protease caspase enzyme