“…In our recent work ( Galiakhmetov et al, 2022 ) we reported on novel highly aligned macrodiscs formed by amphipathic 15-mer peptoid belts, cf. Fig.…”
Section: Introductionmentioning
confidence: 99%
“…The side chains and their relative arrangement can be chosen to mimic SMA co-polymers with the styrene and maleic acid monomers substituted by N -(2-phenylethyl)glycine (Npe) and N -(2-carboxyethyl)glycine (Nce) residues, respectively, incorporated at the 2:1 molar ratio. Unlike SMA, however, the synthesized peptoids have a highly controllable and regular length, which has greatly improved the stability and alignment of the macrodiscs as compared to bicelles and peptide-belt macrodiscs ( Galiakhmetov et al, 2022 ). Fig.…”
“…In our recent work ( Galiakhmetov et al, 2022 ) we reported on novel highly aligned macrodiscs formed by amphipathic 15-mer peptoid belts, cf. Fig.…”
Section: Introductionmentioning
confidence: 99%
“…The side chains and their relative arrangement can be chosen to mimic SMA co-polymers with the styrene and maleic acid monomers substituted by N -(2-phenylethyl)glycine (Npe) and N -(2-carboxyethyl)glycine (Nce) residues, respectively, incorporated at the 2:1 molar ratio. Unlike SMA, however, the synthesized peptoids have a highly controllable and regular length, which has greatly improved the stability and alignment of the macrodiscs as compared to bicelles and peptide-belt macrodiscs ( Galiakhmetov et al, 2022 ). Fig.…”
“…Most recently, an amphiphilic peptoid oligomer with a total of 15 residues arranged in a repeating pattern of two N -2-ethylphenyl glycine followed by one N -2-ethyl carboxyl glycine unit has been synthesized and used to stabilize lipid nanodiscs containing the Pf1 coat protein. The uniformity of the resulting peptoid-stabilized nanodiscs facilitates the solid-state NMR characterization of the trans-membrane protein by enhancing the stability and alignment of nanodiscs under the magnetic field . As a result, we hypothesized that poly[( N -methoxyethyl glycine)- ran -( N -decyl glycine)] random copolypeptoids [ a .…”
Section: Introductionmentioning
confidence: 99%
“…The uniformity of the resulting peptoid-stabilized nanodiscs facilitates the solid-state NMR characterization of the transmembrane protein by enhancing the stability and alignment of nanodiscs under the magnetic field. 33 As a result, we hypothesized that poly[(N-methoxyethyl glycine)-ran-(Ndecyl glycine)] random copolypeptoids [a.k.a. hydrophobecontaining polypeptoids (HCPs)] upon interacting with lipid membranes may adopt an extended polymer conformation with enhanced facial amphiphilicity, thus favoring the formation of polymer belted lipid nanodiscs analogously to the twisted α-helical MSP.…”
Cellular functions of membrane proteins are strongly coupled to their structures and aggregation states in the cellular membrane. Molecular agents that can induce the fragmentation of lipid membranes are highly sought after as they are potentially useful for extracting membrane proteins in their native lipid environment. Toward this goal, we investigated the fragmentation of synthetic liposome using hydrophobe-containing polypeptoids (HCPs), a class of facially amphiphilic pseudo-peptidic polymers. A series of HCPs with varying chain lengths and hydrophobicities have been designed and synthesized. The effects of polymer molecular characteristics on liposome fragmentation are systemically investigated by a combination of light scattering (SLS/DLS) and transmission electron microscopy (cryo-TEM and negative stained TEM) methods. We demonstrate that HCPs with a sufficient chain length (DP n ≈ 100) and intermediate hydrophobicity (PNDG mol % = 27%) can most effectively induce the fragmentation of liposomes into colloidally stable nanoscale HCP−lipid complexes owing to the high density of local hydrophobic contact between the HCP polymers and lipid membranes. The HCPs can also effectively induce the fragmentation of bacterial lipid-derived liposomes and erythrocyte ghost cells (i.e., empty erythrocytes) to form nanostructures, highlighting the potential of HCPs as novel macromolecular surfactants toward the application of membrane protein extraction.
“…Previous studies have demonstrated that a transition from the gel (isotropic) to liquid–crystalline (anisotropic) phase, when the temperature is raised above the phase transition temperature (T m ) of lipids, renders magnetic alignment of nanodiscs such that the bilayer normal is oriented perpendicular to the external magnetic field [ 38 , 42 , 45 , 46 , 47 , 48 , 49 , 50 ]; in addition, a recent solid-state NMR study demonstrated the magnetic alignment of peptoid-based nanodiscs [ 51 ]. When water-soluble molecules are placed in liquid-crystalline nanodiscs, their motion is partially restricted due to the anisotropic environment induced by the aligned nanodiscs [ 21 ].…”
Residual dipolar couplings (RDCs) are increasingly used for high-throughput NMR-based structural studies and to provide long-range angular constraints to validate and refine structures of various molecules determined by X-ray crystallography and NMR spectroscopy. RDCs of a given molecule can be measured in an anisotropic environment that aligns in an external magnetic field. Here, we demonstrate the first application of polymer-based nanodiscs for the measurement of RDCs from nucleic acids. Polymer-based nanodiscs prepared using negatively charged SMA-EA polymer and zwitterionic DMPC lipids were characterized by size-exclusion chromatography, 1H NMR, dynamic light-scattering, and 2H NMR. The magnetically aligned polymer-nanodiscs were used as an alignment medium to measure RDCs from a 13C/15N-labeled fluoride riboswitch aptamer using 2D ARTSY-HSQC NMR experiments. The results showed that the alignment of nanodiscs is stable for nucleic acids and nanodisc-induced RDCs fit well with the previously determined solution structure of the riboswitch. These results demonstrate that SMA-EA-based lipid-nanodiscs can be used as a stable alignment medium for high-resolution structural and dynamical studies of nucleic acids, and they can also be applicable to study various other biomolecules and small molecules in general.
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