Access the “Undruggable” with DIMA Biotech’s Latest Nanodisc

Membrane proteins comprise over half of all drug discovery targets thanks to their essential role in cellular functions and disease processes, inherent druggability, and potential for targeted therapies with minimal off-target effects. In recent years, interest in membrane proteins as therapeutic targets has been further bolstered by advances in structural biology and fresh insights into their three-dimensional structures.

But isolating and purifying membrane proteins for study has been an uphill battle due to their hydrophobicity and structural complexity. With multiple hydrophobic regions, multi-pass transmembrane proteins are particularly prone to aggregation and conformational changes during purification. Many have been called “undruggable” because of these technical challenges, leaving potential targets—and blockbuster interventions—out of reach for certain neurological disorders, cardiovascular diseases, and immunological conditions, to name a few.

But new nanodisc technology from DIMA Biotech promises to bring the undruggable within drug discovery’s grasp. Nanodisc lipid bilayer systems stabilize membrane proteins in a controlled environment, facilitating their structural and functional analysis. The hydrophobic face of the stabilizer interacts with the inner lipid layer, facilitating the integration of membrane proteins into the nanodisc and preserving natural conformation and activity. The hydrophilic side is highly soluble and stable in aqueous solution.

DiMPro^TM, a full-length, multi-pass transmembrane protein-synthetic nanodisc, is the next generation of this technology. At around 10 nm, the disc structure’s diameter maintains the transmembrane proteins in a lipid bilayer—its native membrane environment—so conformation and biological functions are maintained. The polymers used during this process have a dual function: they dissolve the cell membranes, like a detergent would, and also deliver cellular phospholipids that conform nanodisc around the membrane proteins. The target protein, now embedded on the nanodisc, can then be purified by affinity purification.

Notably, DiMPro^TM is free of detergents and membrane scaffold proteins, which can damage protein structures and make the membrane proteins ill-suited for cell-based assays. And unlike membrane scaffold protein nanodiscs, the synthetic DiMPro^TM nanodisc can be prepared directly from the mammalian cells. The use of mammalian cells allows for the incorporation of post-translational modifications, such as glycosylation, which are important for the biological activity of many proteins. These modifications can affect the structure and function of nanodisc proteins, making the mammalian expression system the preferred choice for producing biologically relevant proteins.

By purifying stable, functional, full-length transmembrane proteins for further study, the DiMPro^TM platform will accelerate discovery based on promising, but previously inaccessible, targets. This innovation will also give your lab more time to focus on the biological mechanism and developability study of these important drug targets, ultimately accelerating new drug R&D.

DIMA Biotech provides multiple pre-prepared lead antibody molecules for each target to help pharmaceutical companies skip the tedious steps of monoclonal antibody platform establishment and lead molecule screening.