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
- 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.