Understanding the structure and metabolism of cells and living organisms is essential for the development of new drugs and diagnostics. The availability of chemical tools that allow scientists to edit biomolecules, like proteins, with atom-level resolution have greatly contributed to the progress of chemical biology.
Proteins are macromolecules constructed from a set of twenty chemically different amino acids. One key approach to modify proteins is to react with the sulfur atom in the amino acid cysteine. However, current methods are still problematic in terms of efficiency, selectivity, and stability of the final product (the “adduct”).
Now, the labs of Jérôme Waser and Beat Fierz at EPFL’s Institute of Chemical Sciences and Engineering have developed a new method for modifying cysteines on peptides and proteins. The method uses a group of highly reactive organic molecules, the ethynylbenziodoxolones (EBXs). What makes EBXs highly reactive is that they contain an iodine atom bound to three substituent groups. This non-natural situation leads to high reactivity in these so-called “hypervalent iodine” reagents.
For the first time, the researchers were able to generate a simple biomolecule-EBX adduct while keeping their reactive iodine group in the final molecule. The reaction can be easily performed by a non-expert under standard physiological conditions.