Soluble and stable preparations of purified GPCRs in the absence of detergents are highly desired for enabling the discovery of small-molecule and biological drugs as they would greatly facilitate assay development and structural biology studies. Domainex has refined a generic approach to achieving this goal by using its Polymer Lipid Particle (PoLiPa) technology to stabilise GPCRs; the GPCR is encapsulated in a polymer that encloses a small disc of the native cell membrane lipids.

Advantages of soluble PoLiPa-GPCRs

Enables rapid and generic access to pure samples of GPCRs:

• No mutagenesis
• No detergent
• No refolding
• Generation of pharmacologically intact membrane targets
• Preparations stable over several months
• Versatile applications

PoLiPa-GPCRs are pharmacologically intact and very stable because the protein is enclosed in a disc of functionally important native phospholipids. As such, they can be used across multiple techniques and enable ready access to solution-based drug discovery methods.

Generation of PoLiPa-GPCRs

Applications

• FBDD
• SBDD
• Biophysical characterisation
• Structure determination
• DNA-encoded library screening
• Biological drug hit ID
• Orphan receptor profiling

This methodology was developed in collaboration with Prof. Tim Dafforn, and with funding from the Innovate UK Biocatalyst Award.

For a case study that demonstrates the effectiveness of this approach see Neurotensin receptor 1: Purification by PoLiPa.