The Pentablock Amphiphilic Copolymer T1107 Prevents Aggregation of Denatured and Reduced Lysozyme

Poellmann, Michael J.; Sosnick, Tobin R.; Meredith, Stephen C.; Lee, Raphael C.

doi:10.1002/mabi.201600217

Cited by 5 publications

(6 citation statements)

References 32 publications

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“…In fact, samples exposed to three days of UV were always visibly cloudy to the eye after running aggregation assays. Samples exposed with no UV or lesser amounts of UV exposures showed absorbances at 400 nm that were similar to previous studies [12]. Meanwhile, samples that had high levels of UV exposure (263.6 kGy) showed similar absorbances to the control with no T1107 and PBS.…”

Section: Discussionsupporting

confidence: 86%

“…Previous studies have shown that poloxamine T1107 (T1107) was more effective than poloxamers P188 or P108 as disaggregation catalysts for heat-denatured lysozyme and that 0.1 mM T1107 reduces aggregation of denatured and DTT-reduced HEWL [11,12]. Therefore, in this investigation, we used dithiothreitol (DTT) reduced and HEWL as a model for protein aggregation.…”

Section: Introductionmentioning

confidence: 99%

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Peroxidation of tetronic 1107 reduces protein chaperone effect

Ling¹,

Nguyen²,

McFaul³

et al. 2022

Phys. Biol.

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To enhance the stability of protein therapeutics, pharmaceutical companies have long used various copolymer surfactants as excipients. They act to stabilize proteins by adhering to the hydrophobic surface of the protein preventing denaturation and aggregation. However, some commonly used excipients possess polyoxyalkylene chains that are susceptible to oxidative degradation while in aqueous solution. We postulate that oxidation reactions involving the hydrophobic domains reduce the surfactant’s ability to stabilize the native protein structure. We investigated the effect of UV (λ=254 nm) radiated Poloxamine T1107 (T1107) on its ability to disaggregate DTT denatured hen egg-white lysozyme (HEWL). Peroxidation of UV irradiated T1107 was analyzed using FTIR spectroscopy, the Fe+2 to Fe+3 ion reduction assay method, and 1H NMR. Our results indicate that increased UV irradiation led to structural changes in T1107, specifically the addition of a carbonyl on the formate group. The structural change decreased T1107’s ability to disaggregate HEWL. These results indicate that peroxide content is an important parameter to control in polyoxyalkylene-based excipients.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Peroxidation of tetronic 1107 reduces protein chaperone effect

Ling¹,

Nguyen²,

McFaul³

et al. 2022

Phys. Biol.

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“…González-Gaitano et al [ 41 ] explored the effect of different native and modified cyclodextrins on T904 micelles and revealed that most substituted cyclodextrins induced micellar breakdown while native cyclodextrins promoted the formation of inclusion complexes. Recently, Poellmann [ 42 ] based on his study on T1107 with denatured hen egg white lysozyme found a potential application of T1107 as a synthetic chaperone that enhances the molecular repair phenomenon in cells. Gonzalez-Lopez et al [ 20 ] explored the micellization of different Tetronics ® with varying structural features in acidic media.…”

Section: Introductionmentioning

confidence: 99%

A Comparative Study on Micellar and Solubilizing Behavior of Three EO-PO Based Star Block Copolymers Varying in Hydrophobicity and Their Application for the In Vitro Release of Anticancer Drugs

et al. 2018

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Abstract:The temperature and pH dependent self-assembly of three star shaped ethylene oxide-propylene oxide (EO-PO) block copolymers (Tetronics ® 304, 904 and 908) with widely different hydrophobicity was examined in aqueous solutions. Physico-chemical methods viz. viscosity, cloud point, solubilization along with thermal, scattering and spectral techniques shows strongly temperature and salt dependent solution behavior. T304 possessing low molecular weight did not form micelles; moderately hydrophilic T904 remained as micelles at ambient temperature and showed micellar growth while very hydrophilic T908 formed micelles at elevated temperatures. The surface activity/micellization/solubilization power was favored in the presence of salt. The copolymers turn more hydrophilic in acidic pH due to protonation of central ethylene diamine moiety that hinders micelle formation. The solubilization of a model insoluble azo dye 1-(o-Tolylazo)-2-naphthol (Orange OT) and hydrophobic drugs (quercetin and curcumin) for copolymer solutions in aqueous and salt solutions are also reported. Among the three copolymers, T904 showed maximum solubility of dye and drugs, hence the in vitro release of drugs from T904 micelles was estimated and the effect on cytotoxicity of loading the drugs in T904 micelles was compared with the cytotoxicity of free drugs on the CHO-K1 cells. The results from the present work provide a better insight in selection of Tetronics ® for their application in different therapeutic applications.

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“…41 Similarly, amphiphilic copolymers based on propylene oxide and ethylene oxide were also effective in preventing the aggregation of denatured and reduced lysozyme, and these amphiphilic copolymers can be used as a synthetic chaperone in the innate molecular repair mechanism of cells. 42…”

Section: Introductionmentioning

confidence: 99%

“…For example, triblock copolymers and tetrafunctional block copolymers composed of hydrophobic poly(propylene oxide) and hydrophilic poly(ethylene oxide) chains were reported to reduce the aggregation of the unfolded lysozyme, signifying the importance of a match in size between the hydrophobic region of the denatured protein and that of the amphiphilic copolymer . Similarly, amphiphilic copolymers based on propylene oxide and ethylene oxide were also effective in preventing the aggregation of denatured and reduced lysozyme, and these amphiphilic copolymers can be used as a synthetic chaperone in the innate molecular repair mechanism of cells …”

Section: Introductionmentioning

confidence: 99%

Protein-Stabilizing Effect of Amphiphilic Block Copolymers with a Tertiary Sulfonium-Containing Zwitterionic Segment

Imamura

Mori

2019

ACS Omega

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Tertiary sulfonium-containing zwitterionic block copolymers consisting of N-acryloyl-l-methionine methyl sulfonium salt (A-Met(S+)-OH) and n-butyl acrylate (BA) were newly synthesized to develop a novel protein stabilizer. The zwitterionic block copolymers were prepared by reversible addition–fragmentation chain-transfer (RAFT) polymerization of BA using a hydrophilic macro-chain-transfer agent (CTA) obtained from N-acryloyl-l-methionine (A-Met-OH) and subsequent postmodification. RAFT polymerization of A-Met-OH using poly(BA) macro-CTA, followed by postmodification, also afforded the target poly(A-Met(S+)-OH)-b-poly(BA). The block copolymers stabilized horseradish peroxidase (HRP) during storage at 37 °C for 5 days, and the protein-stabilizing effect was enhanced with increase in the A-Met(S+)-OH content. In particular, the block copolymer with ∼85% A-Met(S+)-OH content showed a significant protein-stabilizing effect at a temperature (37 °C) higher than the room temperature, which is highly desirable for practical and industrial applications. The addition of sucrose into the block copolymer–protein solution led to a considerable increase in the HRP activity under the same conditions. Excellent alkaline phosphatase stabilization at 37 °C for 12 days was also achieved using the block copolymers. The zwitterionic block copolymers with the optimal hydrophilic/hydrophobic balance were found to serve as efficient protein-stabilizing agents, in comparison with the corresponding homopolymer and random copolymers. Dynamic light scattering, zeta potential, transmission electron microscopy, and circular dichroism measurements revealed that the zwitterionic block copolymer stabilizes an enzyme by wrapping with a slight change in the size, whereas the secondary and ordered structures of the enzyme are maintained.

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The Pentablock Amphiphilic Copolymer T1107 Prevents Aggregation of Denatured and Reduced Lysozyme

Cited by 5 publications

References 32 publications

Peroxidation of tetronic 1107 reduces protein chaperone effect

Peroxidation of tetronic 1107 reduces protein chaperone effect

A Comparative Study on Micellar and Solubilizing Behavior of Three EO-PO Based Star Block Copolymers Varying in Hydrophobicity and Their Application for the In Vitro Release of Anticancer Drugs

Protein-Stabilizing Effect of Amphiphilic Block Copolymers with a Tertiary Sulfonium-Containing Zwitterionic Segment

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