Lipid Nanoparticles Make Membrane Proteins Available for Drug Development

A nanoparticle approach that allows researchers to solubilize and then stabilize integral membrane proteins may open the way to 30% more proteins being available as potential targets for drug development.

Membrane proteins, especially receptors that span the cell membrane, are among the most desirable of drug targets. However, difficulties in isolating and stabilizing these proteins have prevented drug developers from making significant progress in this regard. Membrane proteins generally lose their biological activity when the purification process destroys their three-dimensional structure.

Investigators at the University of Birmingham (United Kingdom) and the University of Warwick (United Kingdom) believe they have found a method that solves membrane protein problem. They created bilayer disks formed by phospholipids and styrene maleic anhydride copolymer (SMALPs for short). These nanoparticles are 11 nm in diameter, monodispersed in aqueous solution, biocompatible, and thermostable. A solution containing these particles is able to both solubilize membrane proteins and preserve their functional and structural integrity. These properties, as reported in the May 18, 2009, edition of the Journal of the American Chemical Society (JACS), extend to even alpha-helical and beta-barrel transmembrane proteins.

Senior author Dr. Michael Overduin, professor of structural biology at the University of Birmingham, 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."

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University of Birmingham
University of Warwick