A probe that labels oxidised sulfur atoms in proteins could help researchers studying oxidative stress in living cells. Oxidative stress has been implicated in phenomena as diverse as aging, diabetes and neurodegenerative diseases. 

A group from the University of Michigan in Ann Arbor, US, has developed a probe to follow oxidation of the amino acid cysteine. Kate Carroll, who led the research team, explained: 'We know from genetic studies that bacteria and yeast have finely tuned systems to respond to oxidative assault and that these function through oxidation of pivotal cysteine residues of sentinel proteins.'

Cysteine has a complicated biochemistry, having been found to occur in up to ten different sulfur oxidation states - or oxoforms - including sulfenic acid. 'Our goal,' said Carroll, 'is to develop new approaches to investigate thiol modifications that exploit each cysteine oxoform's unique reactivity for selective recognition.'

With this aim, Carroll's team developed a probe which is chemically selective for protein sulfenic acids. Leslie Poole, a specialist in sulfur biochemistry, at Wake Forest University in North Carolina in the US, described it as 'the first probe demonstrating an ability to trap and detect sulfenic acid formation on proteins within living cells. 'Poole added that 'the small size and cell permeability of this probe enable in situ labelling within cells that can then be followed by linkage to various probes to analyse the sites of modification.'

Outlining the motivation for the work, Carroll said: 'From a biological perspective we were motivated by the knowledge that numerous biological processes could be controlled through relatively modest chemical modification. Adding a single oxygen atom could control whether a cell lives or dies.'

But how cysteine oxidation is linked to disease is not yet clear. Carroll said, 'we must move beyond this stage and understand the biological roles of these modifications for individual proteins at a molecular level. Our long term goal is to investigate the roles that cysteine modifications play in the aging process and in the initiation and progression of disease states, such as cancer.'

The work could also lead to new chemistry. 'From a chemical standpoint, exploring and exploiting differences in reactivity between thiol, sulfenic, sulfinic and sulfonic acid states is also very challenging and exciting,' said Carroll.

Colin Batchelor