Polymer Nanodiscs and Their Bioanalytical Potential

Membrane proteins (MPs) play a pivotal role in cellular function and are therefore predominant pharmaceutical targets. Although detailed understanding of MP structure and mechanistic activity is invaluable for rational drug design, challenges are associated with the purification and study of MPs. Th...

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Bibliographic Details
Published in:Chemistry : a European journal 2021-09, Vol.27 (51), p.12922-12939
Main Authors: Farrelly, Michelle D., Martin, Lisandra L., Thang, San H.
Format: Article
Language:English
Subjects:
amphipathic copolymers
Chemistry
Drug development
Lipids
membrane mimetics
Membrane proteins
Membranes
nanodiscs
Phospholipids
Polymers
Protein interaction
Proteins
styrene maleic acid lipid particles
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Summary:Membrane proteins (MPs) play a pivotal role in cellular function and are therefore predominant pharmaceutical targets. Although detailed understanding of MP structure and mechanistic activity is invaluable for rational drug design, challenges are associated with the purification and study of MPs. This review delves into the historical developments that became the prelude to currently available membrane mimetic technologies before shining a spotlight on polymer nanodiscs. These are soluble nanosized particles capable of encompassing MPs embedded in a phospholipid ring. The expanding range of reported amphipathic polymer nanodisc materials is presented and discussed in terms of their tolerance to different solution conditions and their nanodisc properties. Finally, the analytical scope of polymer nanodiscs is considered in both the demonstration of basic nanodisc parameters as well as in the elucidation of structures, lipid–protein interactions, and the functional mechanisms of reconstituted membrane proteins. The final emphasis is given to the unique benefits and applications demonstrated for native nanodiscs accessed through a detergent free process. Discovering discs: Although understanding membrane protein (MP) structure and activity is invaluable for rational drug design, challenges are associated with purification and analysis of MPs. Synthetic polymer nanodiscs, structures that arise from amphipathic copolymers capturing membrane proteins and surrounding phospholipids, offer a convenient detergent‐free solution. This review explores the scope of possible analytical applications for polymer nanodiscs in the study of MPs and biomolecules.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.202101572