Innovative Polymer Lipid Particle (PoLiPa) Technology

Accelerating G-Protein Coupled Receptor (GPCR) drug discovery

Domainex has established a generic platform for the efficient preparation of stable and highly purified membrane proteins, e.g. GPCRs for use in drug discovery, without the need for thermostabilising mutations or detergents. 

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



  • 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.