Amphiphilic Polymethacrylate Derivatives as Antimicrobial Agents

Kuroda, Kenichi; DeGrado, William F.

doi:10.1021/ja044205+

Cited by 473 publications

(535 citation statements)

References 16 publications

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“…Flexible compounds can be highly potent, possibly because membranes induce an amphiphilic conformation in the bound state (25,40,44). In such cases, additional electrostatic and hydrophobic interactions might be necessary to compensate for the loss in conformational entropy of binding in such compounds.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies reported antibiotics designed to follow the mechanism of natural AMPs, for example, peptides composed of ␣-amino acids (15)(16)(17), ␤-amino acids (18,19), peptoids (20), aromatic oligomers (21)(22)(23)(24), and synthetic polymers (25)(26)(27). Previously, we designed a series of arylamide foldamers that showed potential for both activity and selectivity (21).…”

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confidence: 99%

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De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers

Choi

Isaacs

Clements³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The emergence of drug-resistant bacteria has compromised the use of many conventional antibiotics, leading to heightened interest in a variety of antimicrobial peptides. Although these peptides have attractive potential as antibiotics, their size, stability, tissue distribution, and toxicity have hampered attempts to harness these capabilities. To address such issues, we have developed small (molecular mass <1,000 Da) arylamide foldamers that mimic antimicrobial peptides. Hydrogen-bonded restraints in the arylamide template rigidify the conformation via hydrogen bond formation and increase activity toward Staphylococcus aureus and Escherichia coli. The designed foldamers are highly active against S. aureus in an animal model. These results demonstrate the application of foldamer templates as therapeutics.antibiotic ͉ host defense peptide

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers

Choi

Isaacs

Clements³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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289

323

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“…At first, DeGrado and co-workers successfully fabricated a kind of globally amphiphilic poly(methacrylate) derivatives as antimicrobials by randomly copolymerizing hydrophilic monomers and hydrophobic monomers. 63 After that, as proposed by Stahl and co-workers, the antimicrobial cationic polymers contained cationic and lipophilic subunits and adopted irregular conformations, which could be induced by biomembrane surface into globally amphiphilic conformations. The globally amphiphilic conformation could perform the key roles for considerable antimicrobial activity, as shown in Figure 5.…”

Section: Induced Globally Amphiphilic Conformationmentioning

confidence: 97%

Antimicrobial cationic polymers: from structural design to functional control

Yang

Cai

Huang

et al. 2017

Polym J

212

174

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Antimicrobial cationic polymers mainly contain two functional components: the cationic groups and the hydrophobic groups. The antimicrobial activity is influenced by the type, amount, location and distribution of these two components. This review summarizes the designs and syntheses of antimicrobial cationic polymers by controlling the above two factors. It involves the structural designs from primary to secondary structures, from covalent to noncovalent syntheses and from bulk to surface. Furthermore, it will discuss how to advance structural designs toward functional controls for optimizing the antimicrobial performances and biocompatibility of antimicrobial cationic polymers. It is anticipated that this review will provide some guidelines for developing molecular engineering of antimicrobial cationic polymers with tailor-made structures and functions.

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“…Naturally occurring peptides as well as synthetic mimics including peptoids are known to exhibit antimicrobial activities (47)(48)(49)(50)(51)(52)(53). To test for potential antimicrobial activity of the present aliphatic polyamide dendrimers terminated with amine, cell viability assays using resazurin were performed.…”

Section: Antimicrobial Properties Of Dendrimers and Susceptibility Tomentioning

confidence: 99%

Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers

Jishkariani

MacDermaid

Timsina

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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reviewed by Ezequiel Perez-Inestrosa and Donald A. Tomalia) 2,2-Bis(azidomethyl)propionic acid was prepared in four steps and 85% yield from the commercially available 2,2-bis(hydroxymethyl) propionic acid and used as the starting building block for the divergent, convergent, and double-stage convergent-divergent iterative methods for the synthesis of dendrimers and dendrons containing ethylenediamine (EDA), piperazine (PPZ), and methyl 2,2-bis(aminomethyl)propionate (COOMe) cores. These cores have the same multiplicity but different conformations. A diversity of synthetic methods were used for the synthesis of dendrimers and dendrons. Regardless of the method used, a self-interruption of the synthesis was observed at generation 4 for the dendrimer with an EDA core and at generation 5 for the one with a PPZ core, whereas for the COOMe core, self-interruption was observed at generation 6 dendron, which is equivalent to generation 5 dendrimer. Molecular modeling and molecular-dynamics simulations demonstrated that the observed self-interruption is determined by the backfolding of the azide groups at the periphery of the dendrimer. The latter conformation inhibits completely the heterogeneous hydrogenation of the azide groups catalyzed by 10% Pd/carbon as well as homogeneous hydrogenation by the Staudinger method. These self-terminated polyamide dendrimers are enzymatically and hydrolytically stable and also exhibit antimicrobial activity. Thus, these nanoscale constructs open avenues for biomedical applications.dendrons | ethylenediamine core | piperazine core | antimicrobials | nanomedicine

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Amphiphilic Polymethacrylate Derivatives as Antimicrobial Agents

Cited by 473 publications

References 16 publications

De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers

De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers

Antimicrobial cationic polymers: from structural design to functional control

Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers

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