Simple Derivatization of RAFT-Synthesized Styrene–Maleic Anhydride Copolymers for Lipid Disk Formulations

Burridge, Kevin M.; Harding, Benjamin D.; Sahu, Indra D.; Kearns, Madison M.; Stowe, Rebecca B.; Dolan, Madison T.; Edelmann, Richard E.; Dabney‐Smith, Carole; Page, Richard C.; Konkolewicz, Dominik; Lorigan, Gary A.

doi:10.1021/acs.biomac.0c00041

Cited by 39 publications

(42 citation statements)

References 43 publications

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“…Examples include poly(styrene-co-maleimide) and various amine-modified SMA copolymers, rendering the resulting discs stable at low pH and insensitive to divalent cations. [12][13][14][15][16][17] Other polymers such as poly(diisobutylene-co-maleic acid) (DIBMA) and random polymethacrylate copolymers that are more resistant to divalent cations than SMA have emerged as promising alternative candidate polymers. 18,19 However, the field is limited in terms of controlling the monomer sequence distribution, and molecular weights, an innate limitation in the synthesis of SMA due to the reactivity ratios of STY and MAnh.…”

Section: Introductionmentioning

confidence: 99%

Lipid Nanodiscs via Ordered Copolymers

Smith

Autzen

Faust

et al. 2020

Chem

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A highly alternating copolymer composed of acrylic acid and styrene (AASTY) is synthesized with controlled radical polymerization by exploiting the reactivity ratios of the monomers to control the monomer sequence. The AASTY copolymers are effective solubilizers of cellular membranes and their embedded proteins, which improves structural characterization by single-particle cryo-electron microscopy (cryo-EM). These copolymers are promising tools for exploring detergent-free membrane protein solubilization and direct formation of native nanodiscs, facilitating structural and functional analysis of the mammalian proteome.

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Section: Introductionmentioning

confidence: 99%

Lipid Nanodiscs via Ordered Copolymers

Smith

Autzen

Faust

et al. 2020

Chem

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“…However, no membrane mimetic systems are universally compatible to all membrane proteins requiring rigorous time-consuming optimization processes for their incorporation in a suitable membrane environment. Currently available and widely used membrane mimetic systems are detergent micelles, bicelles, liposomes, lipodiscs, and lipodisq nanoparticles/SMALPs (styrene maleic acid lipid particles) [12][13][14][15][16]. These membrane mimetic systems have their own benefits and limitations.…”

Section: Membrane Proteinsmentioning

confidence: 99%

Probing Structural Dynamics of Membrane Proteins Using Electron Paramagnetic Resonance Spectroscopic Techniques

Sahu

Lorigan

2021

Biophysica

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Membrane proteins are essential for the survival of living organisms. They are involved in important biological functions including transportation of ions and molecules across the cell membrane and triggering the signaling pathways. They are targets of more than half of the modern medical drugs. Despite their biological significance, information about the structural dynamics of membrane proteins is lagging when compared to that of globular proteins. The major challenges with these systems are low expression yields and lack of appropriate solubilizing medium required for biophysical techniques. Electron paramagnetic resonance (EPR) spectroscopy coupled with site directed spin labeling (SDSL) is a rapidly growing powerful biophysical technique that can be used to obtain pertinent structural and dynamic information on membrane proteins. In this brief review, we will focus on the overview of the widely used EPR approaches and their emerging applications to answer structural and conformational dynamics related questions on important membrane protein systems.

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“…A nucleophilic addition to the electrophilic maleic anhydride moiety of SMAnh followed by a ring opening hydrolysis step, has led to the range of polymers shown in Figure 2a) with various R groups modulating the properties of polymers. [23,57] Each of these derivatives attained by nucleophilic addition and ring opening, showed an enhanced viability under lower pH values compared to SMA which aggregates beneath pH~6.3. SMA-Glu and SMA-EA produce copolymers with a negative charge and are active nanodisc agents in pH ranges of above pH~3 and~3.3, respectively.…”

Section: Functionally Modified Smanh Derivatives: Smadsmentioning

confidence: 99%

“…SMA-Glu was shown to best retain protein dynamics by continuous wave electron paramagnetic resonance spectroscopy line-shape analysis. [57] Use of methylamine, ethylamine and propylamine R substituents (SMA-MA, SMA-EtA and SMA-PA) derived from 1 : 1 SMAnh copolymers was found to alter the size and shape of Escherichia coli membrane native nanodiscs. The methylamine substituted polymer assembled into monodispersed nanodiscs of smaller size (~14 nm), while the longer alkyl derivatives formed worm-like nanostructures which tended towards aggregation.…”

Section: Functionally Modified Smanh Derivatives: Smadsmentioning

confidence: 99%

Polymer Nanodiscs and Their Bioanalytical Potential

Farrelly

Martin

Thang

2021

Chemistry A European J

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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, lipidprotein 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.

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Simple Derivatization of RAFT-Synthesized Styrene–Maleic Anhydride Copolymers for Lipid Disk Formulations

Abstract: Peak assignments of the Fourier-transform infrared spectra and solution NMR spectra of the synthesized SMADs and representative TEM images of SMADLPs made from POPC liposomes (PDF)

Cited by 39 publications

References 43 publications

Lipid Nanodiscs via Ordered Copolymers

Lipid Nanodiscs via Ordered Copolymers

Probing Structural Dynamics of Membrane Proteins Using Electron Paramagnetic Resonance Spectroscopic Techniques

Polymer Nanodiscs and Their Bioanalytical Potential

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