Design and Synthesis of Amphiphilic Vinyl Copolymers with Antimicrobial Activity

Foster, Leanna L.; Mizutani, Masato; Oda, Yasukage; Palermo, Edmund F.; Kuroda, Kenichi

doi:10.1002/9781118967904.ch8

Cited by 3 publications

(6 citation statements)

References 61 publications

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“…In general, the thiol group of MMP terminates the propagation of radial polymerization, but the chain termination generates a new thiyl radical, which initiates a new polymerization. 42 Therefore, the molecular weight of polymers depends on the mole ratio of the monomer It should be noted that our polymers are supposed to be called oligomers because of the small molecular size in the polymer science field. However, peptide assemblies with defined structures are generally called ″oligomers″ in the field of peptide science.…”

Section: Resultsmentioning

confidence: 99%

“…The copolymers were synthesized in the presence of chain transfer agent methyl 3-mercaptopropionate (MMP) to give relatively low molecular weights of 1500–2100 g·mol –1 , which are similar to those of AMPs. In general, the thiol group of MMP terminates the propagation of radial polymerization, but the chain termination generates a new thiyl radical, which initiates a new polymerization . Therefore, the molecular weight of polymers depends on the mole ratio of the monomer to MMP.…”

Section: Resultsmentioning

confidence: 99%

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Mechanistic Study of Membrane Disruption by Antimicrobial Methacrylate Random Copolymers by the Single Giant Vesicle Method

et al. 2021

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Cationic amphiphilic polymers have been a platform to create new antimicrobial materials that act by disrupting bacterial cell membranes. While activity characterization and chemical optimization have been done in numerous studies, there remains a gap in our knowledge on the antimicrobial mechanisms of the polymers, which is needed to connect their chemical structures and biological activities. To that end, we used a single giant unilamellar vesicle (GUV) method to identify the membrane-disrupting mechanism of methacrylate random copolymers. The copolymers consist of random sequences of aminoethyl methacrylate and methyl (MMA) or butyl (BMA) methacrylate, with low molecular weights of 1600–2100 g·mol–1. GUVs consisting of an 8:2 mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol), sodium salt (POPG) and those with only 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were prepared to mimic the bacterial (Escherichia coli) or mammalian membranes, respectively. The disruption of bacteria and mammalian cell membrane-mimetic lipid bilayers in GUVs reflected the antimicrobial and hemolytic activities of the copolymers, suggesting that the copolymers act by disrupting cell membranes. The copolymer with BMA formed pores in the lipid bilayer, while that with MMA caused GUVs to burst. Therefore, we propose that the mechanism is inherent to the chemical identity or properties of hydrophobic groups. The copolymer with MMA showed characteristic sigmoid curves of the time course of GUV burst. We propose a new kinetic model with a positive feedback loop in the insertion of the polymer chains in the lipid bilayer. The novel finding of alkyl-dependent membrane-disrupting mechanisms will provide a new insight into the role of hydrophobic groups in the optimization strategy for antimicrobial activity and selectivity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Mechanistic Study of Membrane Disruption by Antimicrobial Methacrylate Random Copolymers by the Single Giant Vesicle Method

et al. 2021

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“…The copolymers were synthesized by free radical polymerization in the presence of 3-methyl mercaptopropionate (MMP) as the chain transfer agent to give low molecular weight polymers (∼2000–3000 g. mol −1 ) as we demonstrated previously. 7 The low molecular weights mimic the small molecular sizes of AMPs. In general, MMP terminates chain propagation, but generate the thiyl radical that initiates new chain propagation.…”

Section: Resultsmentioning

confidence: 99%

“…This chain transfer cycle continues to consume all monomers and gives low molecular weight polymers with high yield. 7 Our previous studies established that 10 mole percent of MMP relative to the total number of monomers were used, which generally gave the polymer with degree of polymerization (DP) of 15–20. 7 This is in good agreement with our current study.…”

Section: Resultsmentioning

confidence: 99%

“… 7 Our previous studies established that 10 mole percent of MMP relative to the total number of monomers were used, which generally gave the polymer with degree of polymerization (DP) of 15–20. 7 This is in good agreement with our current study. 14,18,22,43,49,61,70,73 To facilitate the polymerization in organic solvents and avoid side reactions, the protected monomers ( N -Boc-AEMA and t -butyl PAMA) were used for the polymerization to give Boc-protected precursor polymers.…”

Section: Resultsmentioning

confidence: 99%

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The function of peptide-mimetic anionic groups and salt bridges in the antimicrobial activity and conformation of cationic amphiphilic copolymers

et al. 2021

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Biomimetic antimicrobial polymers—Design, characterization, antimicrobial, and novel applications

Takahashi

Sovadinová

Vemparala

et al. 2022

WIREs Nanomed Nanobiotechnol

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Biomimetic antimicrobial polymers have been an area of great interest as the need for novel antimicrobial compounds grows due to the development of resistance. These polymers were designed and developed to mimic naturally occurring antimicrobial peptides in both physicochemical composition and mechanism of action. These antimicrobial peptide mimetic polymers have been extensively investigated using chemical, biophysical, microbiological, and computational approaches to gain a deeper understanding of the molecular interactions that drive function. These studies have helped inform SARs, mechanism of action, and general physicochemical factors that influence the activity and properties of antimicrobial polymers. However, there are still lingering questions in this field regarding 3D structural patterning, bioavailability, and applicability to alternative targets. In this review, we present a perspective on the development and characterization of several antimicrobial polymers and discuss novel applications of these molecules emerging in the field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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Design and Synthesis of Amphiphilic Vinyl Copolymers with Antimicrobial Activity

Cited by 3 publications

References 61 publications

Mechanistic Study of Membrane Disruption by Antimicrobial Methacrylate Random Copolymers by the Single Giant Vesicle Method

Mechanistic Study of Membrane Disruption by Antimicrobial Methacrylate Random Copolymers by the Single Giant Vesicle Method

The function of peptide-mimetic anionic groups and salt bridges in the antimicrobial activity and conformation of cationic amphiphilic copolymers

Biomimetic antimicrobial polymers—Design, characterization, antimicrobial, and novel applications

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