An affinity for membrane proteins

HERCULES, Calif.—Although approximately 40 percent of today's pharmaceuticals act on proteins such as G protein-coupled receptors (GPCRs) and ion channels that are embedded within cell membranes, determining how drug candidates bind to these proteins is a slow process hindered by the impurity of cell membrane preparations. With these challenges in mind, Bio-Rad Laboratories Inc. and Integral Molecular Inc. have partnered to offer the first system for rapidly and reproducibly characterizing the binding affinities of antibodies to diverse integral membrane proteins.

Under the companies' collaboration agreement, Bio-Rad will use Integral Molecular's proprietary Lipoparticle technology to measure integral membrane protein interactions on its high-throughput ProteOn XPR36 Protein Interaction Array System. The companies will co-market the combined product to their respective customers. Financial terms of the collaboration were not released.

Bio-Rad's ProteOn XPR36 is a multiplexed 6x6 SPR biosensor that allows users to simultaneously measure the interactions of six different ligand proteins with panels of six different concentrations of analyte, obtaining comprehensive kinetic profiles in a single experiment without the need for regeneration, what Bio-Rad terms "One-Shot Kinetics."

Integral Molecular's Lipoparticle technology offers scientists working with membrane-bound targets a standardized reagent with higher concentrations of membrane proteins than cell membrane preparations. Lipoparticles exploit the self-assembling machinery of non-infectious viral core proteins to create non-living, stable, homogenous nanoparticles comprising a lipid bilayer incorporating highly concentrated target receptors. Because the lipid bilayer is derived directly from mammalian cells, the incorporated membrane proteins are structurally intact and correctly oriented.

Customers of the companies can submit sequences of integral membrane proteins to Integral Molecular, which will incorporate the proteins into Lipoparticles and couple them to the ProteOn sensor surface. When used in combination, ProteON and Lipoparticles will enable scientists to rapidly and reproducibly screen membrane protein targeting antibodies for binding characteristics, says Cathy Mainini, senior product manager of Bio-Rad's Protein Function Division.

"These types of membrane proteins present an interesting set of challenges for researchers, and current approaches have only enabled a limited number of membranes to be studied," Mainini says. "Integral Molecular's Lipoparticles are a well-designed, simple, clever and robust solution. The combination of the Lipoparticles with ProteOn allows you to look at the complete kinetic profile of a biomedical interaction on a single chip that allows you to measure 36 different interactions simultaneously without regenerating a single injection of your analyte. What this does is offer our customers a way to be able to successfully measure and monitor native membrane protein targets and their binding partners, generate a huge amount of data and then answer critical questions in hours, rather than days."

The system is ideal for early-stage drug discovery researchers who are interested in rapidly identifying and characterizing monoclonal antibody therapeutics, says Ben Doranz, president and CSO of Integral Molecular.

"Biosensors are used in many parts of the drug discovery, development and diagnostic fields," Doranz says. "ProteOn has quite a few advantages, especially for some of the high-throughput work our customers are interested in. Customers who may really find this combination of technologies really useful will probably be people who are optimizing monoclonal antibodies. This collaboration enables the same kind of work to be done for membrane proteins, at least a third of which are proteins of interest to the biopharmaceutical industry."