Membrane Proteins

Membrane Proteins

Real is Native

Study binding kinetics onto membrane proteins and retain their conformation and activity for more successful drug discovery

Membrane proteins are prime drug targets due to their essential role in regulating physiological processes. Familiar examples include G-protein coupled receptors (GPCR), histidine and tyrosine kinases, and cytokine receptors, in addition to a vast range of ion channels, enzymes, and transporters. With more than half of all currently validated drugs on the market targeting membrane proteins, the importance of this protein family to drug development is well established. However, membrane proteins are notoriously difficult to study, mainly because their hydrophobicity makes them extremely unstable following their extraction from the cell membrane.

Discover new membrane proteins as therapeutic targets

Understanding the interaction between a membrane protein and a small molecule drug or monoclonal antibody therapeutic is fundamental to drug development since it provides valuable insight regarding drug potency and efficacy. Yet to fully understand such liaisons, it is vital that the measurement of binding kinetics between these molecules is reliable. With the sensitivity and versatility to measure analyte-membrane protein interactions in a wide variety of sample matrices, the Creoptix WAVEsystem enables more detailed investigation of membrane protein pharmacology, providing, for example, real-time drug binding affinities and label-free kinetics.

Detergents and other additives can compromise membrane protein integrity

The study of analyte-membrane protein interactions often involves the use of detergents, lipids and other additives to solubilize and purify the protein of interest. These non-native conditions have significant potential to alter the structure and conformation of the membrane protein, as well as impacting analyte-membrane protein binding kinetics, leading to inaccurate interpretation of data.

Virus-like particles, liposomes, and nanodiscs present unique challenges

To avoid the lengthy solubilization and purification processes required to study membrane proteins, researchers often choose to incorporate these biomolecules into a membrane-like environment. This is typically provided by virus-like particles (VLPs), liposomes, or nanodiscs, all of which function to preserve membrane protein integrity and activity. A limitation of this approach is that the resultant size of these structures, combined with a tendency to aggregate, can cause microfluidics channels to clog. Impeded flow may lead to experimental delays and can also increase instrument maintenance costs, however the Creoptix® WAVEsystem overcomes this issue by incorporating a unique, no-clog microfluidic design.

Studying interactions within a membrane context provides greater insight

While some membrane proteins retain their analyte binding activity following solubilization and purification, this is not always the case. It is therefore important to study analyte-membrane protein binding within a membrane context to generate meaningful data. The Creoptix WAVEsystem allows researchers to investigate interactions between large binding partners and membrane proteins while maintaining the latter in their cell membrane environment. This provides essential insights to the binding of antibodies, nanobodies, or Sybody® candidates with the membrane protein of interest, and also allows investigation of membrane protein binding to intracellular signaling partners.

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