Nanoparticles help stabilise proteins for drug development
A new protein stabilisation technique has been developed by scientists that could lead to 30% more proteins being available as potential targets for drug development.
A new protein stabilisation technique has been developed by scientists that could lead to 30% more proteins being available as potential targets for drug development.
Understanding the structure of proteins is a vital first step in developing new drugs, but proteins are difficult to work with in lab conditions due to their instability, However, using nanoparticles, scientists from the Universities of Birmingham and Warwick have found a way to preserve membrane proteins intact, enabling detailed analysis of their structure and molecular functions.
These new findings, which have just been published online in the Journal of the American Chemical Society1, will give scientists access to previously ignored proteins deemed too unstable to work with.
Professor Michael Overduin, from the University of Birmingham, who led the study funded by the Biotechnology and Biological Sciences Research Council (BBSRC), said: "We have shown how a polymer can wrap around and preserve membrane proteins intact in stable nanoparticles. Membrane proteins are the most valuable but technically challenging targets for drug discovery. Finding a gentle solution that preserves their structure and activity, yet is robust enough for experimental interrogation, has eluded scientists for decades, but is now available."
Using a polymer, containing suitable phospholipids - styrene maleic acid lipid particles (SMALPs) - the researchers solubilised a pair of membrane proteins. They found that not only did the proteins maintain their folded structure, binding and enzyme activities in the SMALPs, but also that using the nanoparticles allowed them to be used simply and rapidly, for virtually any laboratory analysis.
Advantages of SMALPs over traditional ways to solubilise proteins such as detergents include enhanced stability, activity and spectral quality of the protein membranes.
Dr Tim Dafforn who jointly ran the study, said: In the past, studies have concentrated largely on soluble proteins as membrane proteins are so difficult to make. However, the discovery of the SMALPs removes this barrier and opens up access to membrane proteins - this has exciting clinical implications as it may enable drug discovery on receptors that are currently too difficult to produce or to study by current methods."