Comb-type Copolymers Research Articles

Controlled Amphiphilicity and Thermo-Responsiveness of Functional Copolymers Based on Oligo(Ethylene Glycol) Methyl Ether Methacrylates.

In this work, comb homopolymers as well as comb-type copolymers of thermo-responsive oligo(ethylene glycol methyl ether methacrylate)s, OEGMAs, with various chain lengths (DEGMA, PEGMA500, and PEGMA950 containing 2, 9, or 19 repeating ethylene glycol units, respectively) were synthesized through free radical (co)polymerization. For the copolymers, either the functional hydrophobic glycidyl methacrylate (GMA) or the inert hydrophilic N,N-dimethylacrylamide (DMAM) were selected as comonomers. The self-assembly and thermo-responsive behavior of the products was investigated through Nile Red fluorescence probing, turbidimetry, and dynamic light scattering (DLS). Interestingly, it was found that all OEGMA-based homopolymers exhibit a tendency to self-organize in aqueous media, in addition to thermo-responsiveness. The critical aggregation concentration (CAC) increases with the number of repeating ethylene oxide units in the OEGMA macromonomers (CAC was found to be 0.003, 0.01, and 0.03% w/v for the homopolymers PDEGMA, PPEGMA500, and PPEGMA950, respectively). Moreover, the CAC of the copolymers in aqueous media is highly affected by the incorporation of hydrophobic GMA or hydrophilic DMAM units, leading to lower or higher values, respectively. Thus, the CAC decreases down to 0.003% w/v for the GMA-richest copolymer of PEGMA950, whereas CAC increases up to 0.01% w/v for the DMAM-richest copolymer of DEGMA. Turbidimetry and DLS studies proved that the thermo-sensitivity of the polymers is governed by several parameters such as the number of repeating ethylene glycol groups in the side chains of the OEGMAs, the molar percentage of the hydrophobic or hydrophilic comonomers, along with the addition of salts in the aqueous polymer solutions. Thus, the cloud point of the homopolymer PDEGMA was found at 23 °C and it increases to 33.5 °C for the DMAM-richest copolymer of DEGMA. Lastly, the formation of a hydrogel upon heating aqueous mixtures of the GMA-comprising copolymers with silica nanoparticles overnight is strong evidence of the functional character of these polymers.

Facilitated belt for ion transport by comb-shape Poly(terphenyl piperidone) carried with macrocyclic crown ether as anchor in anion exchange membrane

To ensure efficient ion transport in anion exchange membranes (AEMs) for hydrogen production, it is essential to develop efficient ion transport pathways. Utilization of intermolecular interactions induced by embedded macrocycles is an attemptable approach. Self-aggregated channels can be constructed with this force serving as a driving force for stepped-up ion transport. Herein, we present a delicate strategy to polymerize the macro crown ether in the backbone and graft flexible alkyl long chains to prepare comb-type copolymers as AEMs. The macrocycle dynamically traps ammonium ions as an anchor which accelerates the aggregation of ionic phases. The resulting AEMs show favorable membrane-forming ability and tensile strength. As the side chain length increases, the microphase-separated morphology develops well and formed ‘belt’-like channels in the poly(terphenyl piperidone)-5-bis-quaternary ammonium (PTCP-5-bisQA) membrane, exhibiting a hydroxide conductivity of 78.1 mS/cm at 80 °C. The alkaline durability of PTCP-5-bisQA AEM is explored by nuclear magnetic hydrogen spectrum (1H NMR) investigation at 80 °C for 720 h. Furthermore, the PTCP-5-bisQA based electrolyzer reaches a current density of 330 mA/cm2 at 1.85V by 1 wt% potassium hydroxide solution circulation. A life endurance observation is carried out on this electrolyzer for a 100h operation with performance degradation rate of 40.1 mV/h.

α-d-(1 → 3)-graft-(1 → 6)-glucan: Comb-like polysaccharide synthesized in vitro with α-1,3/1,6-glucosyltransferase L from Streptococcus salivarius

We demonstrated that a unique polysaccharide with extremely high molecular weight can be easily obtained via a low-cost, mild reaction in a water medium from sucrose, a photosynthetic product. α-1,3/1,6-Glucosyltransferase L (GtfL) from Streptococcus salivarius produced water-insoluble α-d-glucan from sucrose at 37 °C. Gel permeation chromatography revealed the molecular weight was extremely high; the weight-average molecular weight values were more than 1,000,000 irrespective of the substrate concentration. The Smith degradation of neat glucan and NMR spectroscopic analyses of the acetyl derivative revealed a structure similar to that of a comb-type graft copolymer, α-d-(1 → 3)-graft-(1 → 6)-glucan. The anhydroglucose units (AGUs) in the main-chain backbone are linked by (1 → 3)-glycosidic bonds, whereas a side chain consisting of four AGUs via (1 → 6)-glycosidic bonds alternately extends from C6 of the main chain.

Enzyme-Free Signal Amplification Strategy via Chaperone Copolymer-Accelerated Hybridization for Highly Sensitive Detection of Adenosine

Adenosine is a vital biological small molecule that regulates various physiological processes in the human body. A high expression of adenosine in cells can facilitate tumor growth. Therefore, detecting adenosine is crucial for early disease diagnosis. In this paper, we designed a fluorescent biosensor for the sensitive detection of adenosine based on the cationic comb-type copolymer PLL-g-Dex for assisted rapid hybridization of nucleic acids at room temperature. In this strategy, adenosine preferentially binds to the aptamer immobilized on the surface of magnetic nanobeads, releasing free aDNA in solution as the primer strand, which rapidly forms DNA nanowires with auxiliary probes of bDNA with the assistance of PLL-g-Dex. SYBR Green I is embedded in DNA duplexes to generate strong fluorescence. The experimental results showed that PLL-g-Dex promotes DNA hybridization reactions at room temperature to form ultra-long DNA nanowires, thus achieving signal amplification and shortening the detection time. In addition, magnetic nanobeads can reduce the background signal during the reaction. Compared with several previous studies on the fluorescence detection of adenosine, this strategy has a lower detection limit of 2.32 nM. Furthermore, this novel system exhibited a good detection performance even under complex environments, such as serum, providing some reference for the quantitative detection of adenosine in early disease diagnosis.

Malachite green-derivatized cationic comb-type copolymer acts as a photoresponsive artificial chaperone

Molecular chaperones play vital roles in various physiological reactions by regulating the folding and assembly of biomacromolecules. We have demonstrated that cationic comb-type copolymers exhibit chaperone activity for anionic biomolecules including DNA and ionic peptide via the formation of soluble interpolyelectrolyte complexes. The development of smart artificial chaperones that can be spatiotemporally controlled by a remotely guided signal would expand the functions of artificial chaperones. Herein, to enable photocontrol of chaperone activity, a cationic comb-type copolymer bearing malachite green as a photoresponsive unit was designed. We first prepared a series of carboxylic acid derivatives of malachite green identified a derivative that could be quickly and quantitatively converted to the cationic form from the nonionic form by photoirradiation. This derivative was conjugated to the cationic comb-type copolymer, poly(allylamine)-graft-poly(ethylene glycol) through a condensation reaction. Upon photoirradiation, the copolymer bearing 9 mol% malachite green enhanced the membrane disruptive activity of acidic peptide E5 and induced morphological changes in liposomes. This demonstration of photoresponsive activation of chaperoning activity of a copolymer suggests that the installation of carboxyl derivatives of malachite green will impart photoresponsiveness to various materials including biopolymers.

Anionic amphiphilic copolymers as potential agents for enhanced oil recovery

To develop “smart fluids” for enhanced oil recovery from reservoir rocks, comb-type amphiphilic copolymers were synthesized through free radical polymerization (FRP) of: (i) the hydrophilic, anionic monomer 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) that offer a hydrophilic character to the final copolymers; (ii) the weakly acidic hydrophilic monomer acrylic acid (AA); (iii) the hydrophobic monomer dodecyl methacrylate (DMA). The polymers were characterized by Proton Nuclear Magnetic Resonance (1H NMR), Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), fluorescence probing, Dynamic Light Scattering (DLS) and electrophoresis. Stable polymer solutions were prepared without and with the presence of salts (NaCl, CaCl2, MgSO4). The dynamic air/water surface and oil/water interfacial tensions were measured by the pendant drop method, and their steady-state values were estimated with fitting to asymptotic relations predicting the long-time behavior. Moreover, the wettability of water/air and water/oil to glass or poly(methyl methacrylate) (PMMA) surface was quantified by measuring the contact angles. Oil-in-water Pickering emulsions were prepared by mixing n-dodecane with polymer solutions and their stability was evaluated macroscopically with optical inspection, and microscopically by measuring the oil drop size distribution and shear viscosity. Polymer solutions and Pickering emulsions were tested as agents for the displacement of the residual n-dodecane from a glass-etched pore network. The long-lasting retention of polymer solution in the pore network makes the solid surface more hydrophilic, facilitating the fission of oil ganglia into smaller ones which are mobilized easier, resulting in a final EOR efficiency between 10% and 18%. When using an emulsion as displacing fluid, the viscosity ratio and capillary number increase by orders of magnitude, the viscous forces prevail against the capillary ones, and the growth pattern becomes a frontal drive leading to a high EOR efficiency of ∼94%.

Influence of Poly (benzyl oleate-co-maleic anhydride) Pour Point Depressant with Di-Stearyl Amine on Waxy Crude Oil

An important problem for the oil industry is the deposition of paraffin on pipelines during the transit of crude oil and restart processes at low temperature. In this regard, the need for suitable methods of wax deposition has attracted substantial attention. Therefore, pour point depressants (PPDs) are considered a critical processing aid to modify the paraffin crystallization and improve the flow of waxy crude oil. The effect of pendants in comb-type copolymers on the ability of crude oil to flow in the cold is examined in the current study. Such PPDs were first created by the free radical polymerization of maleic anhydride with benzyl oleate to create the poly (benzyl oleate-co-maleic anhydride). The resultant copolymer was then aminated with alkyl amine (stearyl amine) (C18H39N) to form pendant alkyl amine chains. The esterified copolymers were structurally characterized by Fourier Transform Infrared, X-ray diffraction spectral analysis, and scanning electron microscopy. Moreover, the potential interactions between PPD and waxes were investigated by using differential scanning calorimetry, X-ray diffraction, and light microscopy. The obtained PPDs, which are effective at a dose of 2000 ppm, were able to reduce the pour point by up to 3 °C. The viscosity and yield stress of the petroleum waxy crude oil were revealed by rheometer.

Synthesis and characterization of poly[poly(ethylene glycol) methacrylate]-graft-poly(2-vinylpyridine) comb-type graft copolymer using the "grafting through" by free radical polymerization and atom transfer radical polymerization

Synthesis and characterization of poly[poly(ethylene glycol) methacrylate]-graft-poly(2-vinylpyridine) comb-type graft copolymer using the "grafting through" by free radical polymerization and atom transfer radical polymerization

Polymer-functionalized nanoparticles as agents for the in situ remediation of oil-contaminated soils

In-situ flushing of chemicals, such as nanoparticle (NP) suspensions, and NP-based Pickering emulsions, is a well-promising method for the remediation of soils and aquifers contaminated with non-aqueous phase liquids (NAPLs) and the enhanced oil recovery from reservoir rocks. Linear and comb-type copolymers were synthesized by combining (i) hydrophilic, anionic monomers like 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPSA) and acrylic acid (AA) with (ii) hydrophobic monomers like dodecyl methacrylate (DMA). Moreover, polymer-coated nanoparticles (PNPs) was prepared by post-grafting and surface initiated free radical polymerization (FRP) on commercial silica nanoparticles. Dilute dispersions of polymers and PNPs were mixed with salts (NaCl, CaCl2), their dynamic surface and oil/water interfacial tensions were measured by the pendant drop method, and the wettability of all fluid systems to glass surface was quantified by measuring the contact angle. Oil-in-water Pickering emulsions were prepared by dispersing n-dodecane in polymers and n-decane in PNP-colloid with ultrasound probe, and their stability was evaluated by tracking the phase separation and changes of rheological properties, as functions of time. Furthermore, the most stable polymers and PNP-based dispersions and emulsions were chosen and tested as chemicals for the removal of residual oil from a transparent glass-etched pore network.

Effect of Comb-Type Copolymers on the Non-Isothermal Crystallization Behavior of Paraffin in Methyl Ethyl Ketone (MEK)–Toluene Dewaxing

Two comb-type copolymers were synthesized by modifications of the maleic anhydride-α-octadecene copolymer with aniline (AMAC) and with phenethylamine (EMAC), respectively. The effects of AMAC and EMAC on the non-isothermal crystallization kinetics of the MEK–toluene dewaxing process were comparatively investigated. The results showed that, under the optimum process conditions, the addition of 100 ppm AMAC or EMAC could increase the yield of dewaxed oil (DWO) from 67.21% to 70.87% or 69.90%, respectively, and increase the filtration rate by 80% and 70%, respectively. The non-isothermal crystallization kinetics analysis showed that the crystallization process conformed to Mo’s equation, and the addition of AMAC and EMAC slowed down the crystallization rate of paraffin. The polarizing light microscope observations revealed that the addition of AMAC promoted the formation of snow flower-like crystals, and the EMAC addition led to the crystals having longer rods with a relatively complete morphology. This work provided useful experimental data for a better understanding of the roles of comb-type copolymer additives in the MEK–toluene dewaxing process.

Chaperone Copolymer Assisted G-Quadruplex-Based Signal Amplification Assay for Highly Sensitive Detection of VEGF.

Vascular endothelial growth factor (VEGF) is a critical biomarker in the angiogenesis of several cancers. Nowadays, novel approaches to rapid, sensitive, and reliable VEGF detection are urgently required for early cancer diagnosis. Cationic comb-type copolymer, poly(L-lysine)-graft-dextran (PLL-g-Dex) accelerates DNA hybridization and chain exchange reaction while stabilizing the DNA assembly structure. In this work, we examined the chaperone activity of PLL-g-Dex to assist G-quadruplex-based fluorescent DNA biosensors for sensitive detection of VEGF. This convenient and effective strategy is based on chitosan hydrogel, c-myc, Thioflavin T (ThT), VEGF aptamer, and its partially complementary strand. The results show that chaperone copolymer PLL-g-Dex significantly promotes the accumulation of G-quadruplex and assembles into G-wires, allowing an effective signal amplification. Using this method, the detection limit of VEGF was as low as 23 pM, better than many previous works on aptamer-based VEGF detection. This chaperone copolymer-assisted signal amplification strategy has potential applications in the highly sensitive detection of target proteins, even including viruses.

Selective Photo-Crosslinking Detection of Methylated Cytosine in DNA Duplex Aided by a Cationic Comb-Type Copolymer.

In the process of cell development and differentiation, C-5-methylation of cytosine (5-methylcytosine: 5-mC) in genome DNA is an important transcriptional regulator that switches between differentiated and undifferentiated states. Further, abnormal DNA methylations are often present in tumor suppressor genes and are associated with many diseases. Therefore, 5-mC detection technology is an important tool in the most exciting fields of molecular biology and diagnosing diseases such as cancers. In this study, we found a novel photo-crosslinking property of psoralen-conjugated oligonucleotide (Ps-Oligo) to the double-stranded DNA (ds-DNA) containing 5-mC in the presence of a cationic comb-type copolymer, poly(allylamine)-graft-dextran (PAA-g-Dex). Photo-crosslinking efficiency of Ps-Oligo to 5-mC in ds-DNA was markedly enhanced in the presence of PAA-g-Dex, permitting 5-mC-targeted crosslinking. We believe that the combination of PAA-g-Dex and Ps-Oligo will be an effective tool for detecting 5-mC in genomic DNA.

Synthesis and elaboration of modified comb type (maleic anhydride-α-tetradecene) copolymers for cold flow improvers of biodiesel

The maleic anhydride-α-tetradecene copolymer (OMAC) with an approximate relative maleic anhydride to α-tetradecene composition ratio of 1:1.2 was synthesized by free radical copolymerization. The copolymers were modified by the esterification reaction between the anhydride groups and the OH- group of hexadecanol. Comb-type (-maleic acid cetyl ester-co-α-tetradecene-) copolymers (MCEC) with various ratios of alkyl group/carboxyl group (r) were investigated. Upon cooling, the MCEC changed the crystallization state of the wax crystals, and reduced the pour point of the biodiesel, which was observed by pour point and dynamic viscosity testing. The MCEC efficiency that improved the cold flow properties of the biodiesel was found to be correlated to r. MCEC with r=2.76 was found to be the most effective in improving the flow ability of the palm oil biodiesel. Our study demonstrates the ability of MCEC3 at 1000 ppm concentration to reduce the pour point of palm oil biodiesel to 10.5oC and the dynamic viscosity up to 1.04 mPa.s. A correlation was found between the number and the length of the pendant alkyl groups of additives and the compositions of the fatty acid methyl ester of the biodiesel.

A new analytical approach for preconcentration, separation and determination of Pb(II) and Cd(II) in real samples using a new adsorbent: Synthesis, characterization and application

A green and efficient analytical approach was reported for simultaneous preconcentration, and separation of Pb(II) and Cd(II) in water, vegetables, and barbecue samples by dispersive solid-phase microextraction prior to their determination using flame atomic absorption spectrometry. A new poly-3-hydroxy butyrate-polyvinyl triethyl ammonium chloride comb-type amphiphilic cationic block copolymer (PHBvbNCl) was synthesized and characterized. Main variables such as pH, sorbent amount, adsorption time, eluent type, desorption time, and sample volume were optimized. Detection limits and working ranges for Pb(II) and Cd(II) were 0.03 μg L-1, 0.15 μg L-1, 0.1–250 μg L-1 and 0.5–375 μg L-1, respectively. Enhancement factor for Pb (II) and Cd (II) were 114 and 98. The adsorption capacity of PHBvbNCl for Pb(II) and Cd(II) was 175.2 mg g−1 and 152.9 mg g−1. After the accuracy of the method was confirmed by the analysis of certified reference materials, it was successfully applied to real samples. Finally, the analytical performance of the present method was compared with other methods.

Synthesis and characterization of comb-type graft copolymers by redox polymerization and "click" chemistry method

The synthesis of poly(epichlorohydrin-g-methyl methacrylate) [poly(ECH-g-MMA)] comb-type graft copolymers were carried out by use of a click chemistry to graft terminally propargyl poly(methyl methacrylate) (PMMA-propargyl) to poly(epichlorohydrin) azido (PECH-N3). For this purpose, PECH-N3 was synthesized by using poly(epichlorohydrin) and sodium azide. PMMA-propargyl was obtained by reaction of methyl methacrylate and propargyl alcohol via redox polymerization technique. By using PECH-N3 and PMMA-propargyl, the comb-type graft copolymers were obtained. Characterization of the modified homopolymers and the comb-type graft copolymers was performed by using FT-IR, 1H-NMR, SEM, GPC, and elemental analysis techniques. Thermal transitions and degradation features of the comb-type graft copolymers were investigated by using DSC and TGA methods. Spectroscopic and thermal analyses revealed that both group modifications and coupling reactions were successfully achieved.

Dispersion of different carbon-based nanofillers in aqueous suspension by polycarboxylate comb-type copolymers and their influence on the early age properties of cementitious matrices

The dispersion behaviour of different carbon-based nanofillers in deionized (DI) water was investigated in the study at hand by using polycarboxylates as surfactants. Carbon nanotubes (CNTs), carbon black (CB) and expanded graphite (EG) were firstly characterized in respect of their morphology. Subsequently, they were dispersed in DI water using two polycarboxylate (PCE) comb-type copolymers which differed in length of their chemical backbones. Optical microscopy and light transmission analysis during centrifugation disclosed a clear difference in the dispersibility among the nanofillers under investigation. Small CB particles showed excellent dispersion in DI water even with no surfactant. CNT was dispersed significantly better than EG, whereby the PCE with the longer backbone yielded better filler dispersion in both cases. After incorporating the carbon nanofillers into a cementitious matrix, interestingly, the highest compressive and flexural strengths at an early age were measured for the CNT samples with worse filler dispersion. This effect is explained by the role of the PCE and the aspect ratio of the carbon nanofiller, both of which determine the microstructure in the hardened cement-based matrix collaboratively.

Hydrophobic-hydrophilic comb-type quaternary ammonium-functionalized SEBS copolymers for high performance anion exchange membranes

Poly(styrene-b-ethylene-co-butylene-b-styrene) (SEBS) triblock copolymers are prepared with 50% hexyl quaternary ammonium (HQA) and 20% alkyl chains of different chain lengths: C4 (50HQA-20C4-SEBS) and C12 (50HQA-20C12-SEBS). Their physicochemical and electrical properties are investigated for use as novel alkaline anion exchange membranes. In most other comb-type polymers, the alkyl chain is introduced as a hydrophilic spacer unit between the polymer backbone and conducting head group. In the current study, additional alkyl chains are grafted onto the SEBS polymer as hydrophobic side chains as well as typical hydrophilic side chains. Introduction of this extra hydrophobic alkyl spacer group is done to obtain well-connected morphology, increased free volume, enhanced water uptake and related conductivity, together with improved physicochemical properties of the membranes obtained. The results are compared with HQA-functionalized SEBS without the hydrophobic alkyl spacer group (50HQA-20C0-SEBS), and the effects of the alkyl chain lengths on the structure of polymers and physicochemical properties of the corresponding membranes are investigated.

Synthesis of comb-type block copolymers by grafting through method: electrical properties and determination of activation energy via conductivity

Poly[Ɛ-CL-b-(MMA-comb-EMA)]comb-type polymers were synthesized by ATRP and Ɛ-caprolactone macroinitiator and macromonomer. Methyl methacrylate macromonomer was synthesized from acylation reaction of methacryloyl chloride with PMMA ended 7-hydroxy coumarin. The macroinitiator was prepared from the reaction of chlorine acetyl chloride P(Ɛ-CL). The synthesized polymers were characterized by FT-IR, 1H-NMR and 13C-NMR techniques. The average molecular weight and molecular weight distribution of polymers were measured by GPC method. Thermal properties of samples were studied by DSC/TGA techniques. Dielectric and Ac conductivity measurements were performed. Dielectric constant (ɛˈ), dielectric loss factor (ɛˈˈ) and conductivity behaviors of comb-type polymer were measured at room temperature between the frequency of 100–2000 Hz and over the temperature range 303–413 K at 1 kHz reported as compared with each other. Besides, their effects on the electrical properties by doping with EuCl3 for some of the comb copolymers were and were investigated. The activation energy (Ea) was calculated from conductivity. We reported it was determined that the (ɛˈ) and (ɛˈˈ) values decreased with increasing frequency. There are also many application areas for comb polymers for example; nanotechnology, medicine. The aim of this study is to synthesize comb-type copolymers in different compositions and to investigate their electrical properties.

Cationic comb-type copolymer as an artificial chaperone

Accurate folding of biopolymers and assembly of complexes containing these molecules are essential for biological activities. We designed cationic comb-type copolymers that act as an artificial chaperone to assist in the folding of biopolymers such as nucleic acids and peptides. The copolymers consist of a polycation backbone grafted with a high density of hydrophilic chains that allow the formation of soluble and soft interpolyelectrolyte complexes between the copolymer and oppositely charged biopolymers. The copolymers can chaperone DNA assembly into duplex, triplex, and quadruplex structures and accelerate strand exchange reactions while stabilizing DNA complexes. This chaperone activity of the copolymer is useful in nucleic acid-based nanotechnological applications such as DNA nanomachines, DNA logic gates, and DNA enzymes. The cationic comb-type copolymers also assisted in the folding of functional peptides. The basic E5 peptide folds into an alpha-helical structure and exhibits a stronger membrane-disrupting activity in the presence of the copolymer than in its absence. The cationic comb-type copolymers, as an artificial chaperone, were shown to be beneficial for enhancing the functions and facilitating the application of biopolymers in nanotechnology and medicine. The cationic comb-type copolymers, which consisted of a polycation backbone grafted with high density of hydrophilic chains, form soluble and soft interpolyelectrolyte complexes with biopolymers and act as an artificial chaperone to assist in the folding of nucleic acids and peptides. The copolymers stabilize DNA duplex, triplex, and quadruplex structures and accelerate strand exchange reactions as well as assist in the folding of functional peptides into the active conformation.

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.