Turning Proteins into the Strongest Known Acids to Improve Detection

Posted 5 May 2017

The strongest organic acid ever has been produced by chemists at UNSW, and it is set to revolutionise protein analysis by mass spectrometry.

“We’ve discovered how to form protein ions in really highly-charged states, so reactive that they can transfer a proton to molecules and atoms that are normally considered inert, like argon and nitrogen,” says Dr W. Alex Donald, who led the research. These protein ions are more acidic than fluroantimonic acid, the strongest acid on record until now.

Protein analysis is primarily achieved by mass spectrometry, and more highly-charged proteins can be more readily characterised and sequenced.

With this new method of forming highly-charged protein ions, the sequences of most proteins can be completely and rapidly characterise, not just small ones under 10 kilodaltons, which is the limit of existing mass spectrometry technology. This is useful for characterising how proteins are chemically modified post-translation – modifications that can entirely alter protein functions, sometimes leading to disease, explains Donald.

This research was carried out primarily by Muhammad Zenaidee, a PhD student in the Donald research group, and published in the premier chemistry journal, Angewandte Chemie International Edition, on 4 May 2017. The research communication made such an impact during peer-review that the journal has designated it a Very Important Paper – an honour that less than 5% of their publications receive.

Donald’s breakthrough resolves a longstanding debate in the mass spectrometry field about how protein ions are formed in electrospray ionization, a Nobel Prize-winning technology. This could change the way that mass spectrometers are designed.

By modification of the ion source, protein ions in even higher charge states could be generated to produce better sensitivity, improve protein sequence coverage, and speed up protein analysis.

“If you understand how something works, in principal, you should be able to make it work better,” says Donald.

[Above image: Highly-charged protein ions can protonate noble gases, such as Argon (Ar), in ambient temperature. Protein ion “super acids” are formed using electrospray ionization “supercharging” which transfers proteins from solution (represented by fish) to the gas phase (birds)]