Labeling Of The Peptides And Proteins

Proteins are macromolecules constructing; from a set of twenty chemically different amino acids. One key approach to modifying proteins and peptides is to reacting with the sulfur atom in the amino acid cysteine. Understanding the structure and metabolism of cells and living organisms; is essential for the development of new drugs and diagnostics.

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. 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.

Peptides and proteins

One new functionality can be introduced via ‘click-chemistry’; a well-established reaction in chemical biology,” says Waser. “Using a palladium catalys, another selective modification can be achieved at the reactive iodine atom- what we would call a ‘biorthogonal’ functionality, as it does not exist in nature.

But 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 performing by a non-expert under standard physiological conditions. The end product are protein-hypervalent iodine reagent chimeras; that can act as dual attachment points for two new chemical groups, opening up new opportunities for the study of biological processes.

Photoprotecting group

But exotic reactive groups into biomolecules is currently one of the most important tools in chemical biology, as it allows the study of biological processes without interfering with them. For example, the scientists used the dual handle to attach a fluorescent dye and a photoprotecting group into a neuropeptide simultaneously.

But by combining them improves the dye’s photostability, and enables high-resolution, single-molecule imaging of molecular interactions. Beyond peptides, they further modified small proteins, and even large protein-DNA complexes, so-called nucleosomes. As nucleosomes organize the genome, labeling them with fluorescent dyes can help track them to decipher how nature regulates gene expression.