Cationic Copolymers Act As Chaperones of a Membrane-Active Peptide : Influence on Membrane Selectivity
Membrane-active peptides have potential as drug delivery tools for control of lipid bilayer structures in cells and liposomes. In a previous study, we reported that a cationic comb-type copolymer, poly(allylamine)-graft-dextran (PAA-g-Dex), forms a soluble interpolyelectrolyte complex with an anionic peptide, E5, and enhances its membrane-disrupting activity. Furthermore, the E5/PAA-g-Dex complex augments the cellular membrane permeability of other proteins. In this study, the affinities of the E5/PAA-g-Dex complex for lipid membranes with various compositions were determined. Secondary structure analysis of E5 and analyses of binding of E5 to liposomes revealed that lipid composition strongly influenced the interaction. No significant folding of E5 alone was observed at either pH 5.4 or pH 7.4 and folding into the functional conformation, which is both N-terminal and C-terminal helix, was observed only at pH 5.4 in the presence of liposomes having liquid-disordered phase (Ld). PAA-g-Dex induced partial folding of E5, presumably at C-terminus, at both pH 5.4 and pH 7.4. Folding of E5 into the functional structure was induced by the addition of liposomes having Ld phases at either pH 5.4 or pH 7.4. A leakage assay showed that PAA-g-Dex enhanced the membrane-permeabilizing activity of E5 by promoting the adsorption of E5 onto the surface of liposomes and/or E5 association with the lipid bilayer. These results indicated that E5 activated by PAA-g-Dex destabilizes the lipid membrane having Ld phase even when the lipid membrane has a heterogeneous phase separated structure. Hence, PAA-g-Dex serves as a chaperone for E5 without altering its membrane selectivity. The chaperoning activity of this comb-type copolymer may activate other ionic peptides with unstable structures and low solubility.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
ACS biomaterials science & engineering - 5(2019), 11 vom: 11. Nov., Seite 5744-5751 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sakamoto, Wakako [VerfasserIn] |
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| Links: |
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| Themen: |
Cationic copolymer |
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| Anmerkungen: |
Date Revised 14.01.2021 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1021/acsbiomaterials.8b01582 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Membrane-active peptides have potential as drug delivery tools for control of lipid bilayer structures in cells and liposomes. In a previous study, we reported that a cationic comb-type copolymer, poly(allylamine)-graft-dextran (PAA-g-Dex), forms a soluble interpolyelectrolyte complex with an anionic peptide, E5, and enhances its membrane-disrupting activity. Furthermore, the E5/PAA-g-Dex complex augments the cellular membrane permeability of other proteins. In this study, the affinities of the E5/PAA-g-Dex complex for lipid membranes with various compositions were determined. Secondary structure analysis of E5 and analyses of binding of E5 to liposomes revealed that lipid composition strongly influenced the interaction. No significant folding of E5 alone was observed at either pH 5.4 or pH 7.4 and folding into the functional conformation, which is both N-terminal and C-terminal helix, was observed only at pH 5.4 in the presence of liposomes having liquid-disordered phase (Ld). PAA-g-Dex induced partial folding of E5, presumably at C-terminus, at both pH 5.4 and pH 7.4. Folding of E5 into the functional structure was induced by the addition of liposomes having Ld phases at either pH 5.4 or pH 7.4. A leakage assay showed that PAA-g-Dex enhanced the membrane-permeabilizing activity of E5 by promoting the adsorption of E5 onto the surface of liposomes and/or E5 association with the lipid bilayer. These results indicated that E5 activated by PAA-g-Dex destabilizes the lipid membrane having Ld phase even when the lipid membrane has a heterogeneous phase separated structure. Hence, PAA-g-Dex serves as a chaperone for E5 without altering its membrane selectivity. The chaperoning activity of this comb-type copolymer may activate other ionic peptides with unstable structures and low solubility | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cationic copolymer | |
| 650 | 4 | |a chaperones | |
| 650 | 4 | |a lipid membrane | |
| 650 | 4 | |a membrane permeabilization | |
| 650 | 4 | |a membrane-active peptides | |
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| 700 | 1 | |a Ochiai, Takuro |e verfasserin |4 aut | |
| 700 | 1 | |a Shimada, Naohiko |e verfasserin |4 aut | |
| 700 | 1 | |a Maruyama, Atsushi |e verfasserin |4 aut | |
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