UK scientists have developed a more sensitive technique for studying how peptides unfold. They expect that the method will be useful in fundamental research on protein structure and in understanding conditions such as Alzheimer's disease.

Ewan Blanch from the University of Manchester and his colleagues used Raman spectroscopy to analyse protein model poly(glutamic acid) as it unfolded in response to increasing pH. The scientists discovered two distinct phases as poly(glutamic acid) goes from the helical to the disordered state. They speculate that this is because the end and central helix regions have different thermodynamic stabilities.

The group combined normal and chiral Raman spectroscopies to examine the protein model. Both methods have been used for some years to study protein unfolding, but correlating the two techniques has proved to be advantageous for two reasons, said Blanch. 'Firstly, you get much better spatial resolution, allowing you to resolve smaller spectral bands,' he said. 'Secondly, you can see which bands in a spectrum behave in the same way as experimental conditions change. If we know the origins of these bands we can map out the series of changes that occurs during an experiment and learn something new about the mechanisms involved.'

Raman spectroscopy can be used to study proteins as they unfold

The technique can very easily be applied to more complex systems, said Blanch; co-worker Lorna Ashton has used it to study the unfolding of real proteins. The group will also use the method to investigate RNA unfolding and the formation of amyloid fibrils, protein aggregates associated with Alzheimer's disease and many other conditions.

'We are just beginning to explore the potential of Raman and correlation analysis,' said Blanch. 'We encourage fellow scientists to try them.'

Danièle Gibney