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1. Extraction and reconstitution of membrane proteins into lipid nanodiscs encased by zwitterionic styrene-maleic amide copolymers

   https://doi.org/10.1038/s41598-020-66852-7  

   Fiori, Mariana C. ; Zheng, Wan ; Kamilar, Elizabeth ; Simiyu, Geuel ; Altenberg, Guillermo A. ; Liang, Hongjun ( June 2020 , Scientific Reports)

   Membrane proteins can be reconstituted in polymer-encased nanodiscs for studies under near-physiological conditions and in the absence of detergents, but traditional styrene-maleic acid copolymers used for this purpose suffer severely from buffer incompatibilities. We have recently introduced zwitterionic styrene-maleic amide copolymers (zSMAs) to overcome this limitation. Here, we compared the extraction and reconstitution of membrane proteins into lipid nanodiscs by a series of zSMAs with different styrene:maleic amide molar ratios, chain sizes, and molecular weight distributions. These copolymers solubilize, stabilize, and support membrane proteins in nanodiscs with different efficiencies depending on both the structure of the copolymers and the membrane proteins.

    

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2. Alternatives to Styrene‐ and Diisobutylene‐Based Copolymers for Membrane Protein Solubilization via Nanodisc Formation

   https://doi.org/10.1002/anie.202306572  

   Workman, Cameron E. ; Bag, Pushan ; Cawthon, Bridgie ; Ali, Fidaa H. ; Brady, Nathan G. ; Bruce, Barry D. ; Long, Brian K. ( September 2023 , Angewandte Chemie International Edition)

   Styrene‐maleic acid copolymers (SMAs), and related amphiphilic copolymers, are promising tools for isolating and studying integral membrane proteins in a native‐like state. However, they do not exhibit this ability universally, as several reports have found that SMAs and related amphiphilic copolymers show little to no efficiency when extracting specific membrane proteins. Recently, it was discovered that esterified SMAs could enhance the selective extraction of trimeric Photosystem I from the thylakoid membranes of thermophilic cyanobacteria; however, these polymers are susceptible to saponification that can result from harsh preparation or storage conditions. To address this concern, we herein describe the development of α‐olefin‐maleic acid copolymers (αMAs) that can extract trimeric PSI from cyanobacterial membranes with the highest extraction efficiencies observed when using any amphiphilic copolymers, including diisobutylene‐co‐maleic acid (DIBMA) and functionalized SMA samples. Furthermore, we will show that αMAs facilitate the formation of photosystem I‐containing nanodiscs that retain an annulus of native lipids and a native‐like activity. We also highlight how αMAs provide an agile, tailorable synthetic platform that enables fine‐tuning hydrophobicity, controllable molar mass, and consistent monomer incorporation while overcoming shortcomings of prior amphiphilic copolymers.

    

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3. Alternatives to Styrene‐ and Diisobutylene‐Based Copolymers for Membrane Protein Solubilization via Nanodisc Formation

   https://doi.org/10.1002/ange.202306572  

   Workman, Cameron E. ; Bag, Pushan ; Cawthon, Bridgie ; Ali, Fidaa H. ; Brady, Nathan G. ; Bruce, Barry D. ; Long, Brian K. ( September 2023 , Angewandte Chemie)

   Styrene‐maleic acid copolymers (SMAs), and related amphiphilic copolymers, are promising tools for isolating and studying integral membrane proteins in a native‐like state. However, they do not exhibit this ability universally, as several reports have found that SMAs and related amphiphilic copolymers show little to no efficiency when extracting specific membrane proteins. Recently, it was discovered that esterified SMAs could enhance the selective extraction of trimeric Photosystem I from the thylakoid membranes of thermophilic cyanobacteria; however, these polymers are susceptible to saponification that can result from harsh preparation or storage conditions. To address this concern, we herein describe the development of α‐olefin‐maleic acid copolymers (αMAs) that can extract trimeric PSI from cyanobacterial membranes with the highest extraction efficiencies observed when using any amphiphilic copolymers, including diisobutylene‐co‐maleic acid (DIBMA) and functionalized SMA samples. Furthermore, we will show that αMAs facilitate the formation of photosystem I‐containing nanodiscs that retain an annulus of native lipids and a native‐like activity. We also highlight how αMAs provide an agile, tailorable synthetic platform that enables fine‐tuning hydrophobicity, controllable molar mass, and consistent monomer incorporation while overcoming shortcomings of prior amphiphilic copolymers.

    

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4. Tunable, biodegradable grafting-from glycopolypeptide bottlebrush polymers

   https://doi.org/10.1038/s41467-021-26808-5  

   Clauss, Zachary S. ; Wardzala, Casia L. ; Schlirf, Austin E. ; Wright, Nathaniel S. ; Saini, Simranpreet S. ; Onoa, Bibiana ; Bustamante, Carlos ; Kramer, Jessica R. ( November 2021 , Nature Communications)

   The cellular glycocalyx and extracellular matrix are rich in glycoproteins and proteoglycans that play essential physical and biochemical roles in all life. Synthetic mimics of these natural bottlebrush polymers have wide applications in biomedicine, yet preparation has been challenged by their high grafting and glycosylation densities. Using one-pot dual-catalysis polymerization of glycan-bearing α-amino acidN-carboxyanhydrides, we report grafting-from glycopolypeptide brushes. The materials are chemically and conformationally tunable where backbone and sidechain lengths were precisely altered, grafting density modulated up to 100%, and glycan density and identity tuned by monomer feed ratios. The glycobrushes are composed entirely of sugars and amino acids, are non-toxic to cells, and are degradable by natural proteases. Inspired by native lipid-anchored proteoglycans, cholesterol-modified glycobrushes were displayed on the surface of live human cells. Our materials overcome long-standing challenges in glycobrush polymer synthesis and offer new opportunities to examine glycan presentation and multivalency from chemically defined scaffolds.

    

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5. Employing Heterocyclic Hypervalent Iodine Compounds with ICl Bonds as Initiators and Chain Transfer Agents in the Synthesis of Branched Polymers

   https://doi.org/10.1002/macp.201800471  

   Cao, Yakun ; Kumar, Rajesh ; Tsarevsky, Nicolay V. ( January 2019 , Macromolecular Chemistry and Physics)

   Heterocyclic hypervalent (HV) iodine(III) compounds with ICl bonds and various substituents at the N atom are synthesized and found to be very efficient chain transfer agents in the polymerization of styrene with transfer coefficients exceeding that of CCl₄by 2–3 orders of magnitude, depending on the structure. The chain transfer rate coefficients are also determined. Due to the presence of thermally labile HV bonds, the compounds degrade homolytically upon heating and can initiate radical polymerization. For instance, 1‐chloro‐2‐hexyl‐1,2‐benziodazol‐3(2H)‐one, is used in the polymerization of styrene, which yields low molecular weight polymers with alkyl chloride groups at the α‐ (initiation) and the ω‐chain ends (transfer). Chain‐end functionalization reactions with azide and chain extension under low‐catalyst‐concentration atom transfer radical polymerization (ATRP) conditions of the prepared telechelic polymers are carried out. The same initiator/chain transfer agent is successfully employed in the synthesis of highly branched polymers with multiple alkyl chloride‐type chain ends when added to mixtures of styrene and 1,4‐divinylbenzene containing 10–80 mol% of the divinyl crosslinker, or even pure crosslinker. In all cases, soluble hyperbranched polymers are obtained up to moderate monomer conversions. The effects of crosslinker and HV iodine(III) compound concentrations on the polymerization outcome are studied systematically.

    

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