In comparison to soluble proteins, the study of MPs has long been problematic due to difficulties in their isolation in an intact and functional form. The isolation of MPs from cell membranes has traditionally been carried out by the interaction of the membranes with surfactants/detergents. This method has significant shortcomings when it comes to functionality and stability of certain MPs. MPs are major molecular targets used in drug discovery as well as in validation of available drugs, therefore the ability to maintain the structural integrity of these MPs is paramount for accurate drug design.
More recently, it was discovered that the poly(styrene-co-maleic acid) (SMA) polymer is able to isolate MPs with a layer of closely associated native phospholipids in nanoscale discs, called nanodiscs. SMA and similar polymers act as molecular cookie cutters to isolate MPs in their natural phospholipid environment, leading to improved functionality and stability of the MPs.
Although the use of commercial SMA has led to significant improvement in the isolation of MPs, there are still shortcomings of this technology, such as limited stability in the presence of divalent cations (Ca2+, Mg2+, etc.), limited stability at low and high pH, and low-resolution separation in gel electrophoresis (SDS-PAGE), also known as “smearing”.
The primary difference between the commercial variants and the polymers produced through this technology, is the synthetic approach utilised. The current technology features polymers that are made via controlled polymerization methods, whereas commercial variants are made by conventional radical polymerization techniques. The polymers produced by these controlled techniques offer several advantages over commercially available polymers and are effective synthetic strategies to produce polymers with well-defined architecture, controlled molecular weight and molecular weight distributions while affording “living characteristics” to the polymers. The chain ends of polymers made via this approach, inherently contain chain-end functionality which allows for selective post-polymerization modifications. These modifications include the attachment of certain tags and/or probes e.g. fluorescent, biotin, etc. which may prove very useful for downstream applications. The well-defined structural properties of the polymers obtained via this technique facilitates systematic studies used to understand the mode of action and complex interplay between the polymer and the isolated MP.
The production of polymers via controlled polymerizations, enables the design and synthesis of new, functional polymers that outperform conventional methods while offering customization possibilities for integration into current workflow methodologies. These benefits will facilitate more successful drug target identification.
Prof Bert Klumperman, Department of Chemistry and Polymer Science, Faculty of Science
Gestél Kuyler, Department of Chemistry and Polymer Science, Faculty of Science
Yes – We are looking for channel partners and collaborators to elevate this outstanding technology and make it the new norm in membrane protein research.
We are aiming to acquire pre-seed funding for commercial expansion in terms of equipment upgrade within the next 6 months.