High Potency and Broad-Spectrum Antimicrobial Peptides Synthesized via Ring-Opening Polymerization of α-Aminoacid-<i>N</i>-carboxyanhydrides

Zhou, Chuncai; Xiang-yang, QI; Li, Peng; Chen, Wei Ning; Lamrani, Mouad; Chang, Matthew Wook; Leong, Susanna Su Jan; Chan‐Park, Mary B.

doi:10.1021/bm900896h

Cited by 154 publications

(152 citation statements)

References 55 publications

(92 reference statements)

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“…14 Polypeptides consisting of a combination of lysine, alanine, phenylalanine, and leucine amino acids were prepared via the NCA-ROP technique, and the synthetic polypeptides showed microbiocidal activity against a wide range of pathogenic microorganisms, including clinically significant bacteria Serratia marcescens and fungi Candida albicans. 15 Under a transmission electron microscopy study, micelles consisting of a poly(L-lactide) core and poly( phenylalanine-stat-lysine) shell were reported to readily pierce and destroy the membrane of Gram-negative and Gram-positive bacteria. 16 However, it should be noted that synthetic cationic peptides are often toxic and detrimental to mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

Pranantyo

Zheng

et al. 2017

Polym. Chem.

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A series of four-arm star copolymers, incorporating glycopolymer and antimicrobial polypeptide domains, was developed in the design of forthcoming anti-infective agents. Mannose, glucose, and galactosebased glycopolymers with a variety of well-defined chain lengths were prepared via atom transfer radical polymerization, whereas linear α-polylysine was prepared via ring-opening polymerization of N-carboxyanhydride monomers. Copper-catalyzed azide-alkyne cycloaddition was employed for 'click' conjugation of the glycopolymer arms and the polypeptide chains. The glycopolymer-polypeptide conjugates were non-hemolytic and exhibited higher cytocompatibility than the linear α-polylysine. The conjugates with shorter chains of mannose-based glycopolymer arms showed an enhanced bactericidal efficacy against Gram-negative and Gram-positive bacteria, with a therapeutic selectivity half of that of the linear α-polylysine. The pendant mannose moieties of the conjugates increased microbial targeting due to their specific affinity for bacterial surfaces, and binding competition with free mannopyranoside was demonstrated. Therefore, the molecular combination of glycopolymers and polypeptides without loss of their respective activities provides an interesting concept in the design of antimicrobial agents to combat infectious disease.

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Section: Introductionmentioning

confidence: 99%

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

Pranantyo

Zheng

et al. 2017

Polym. Chem.

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“…There has also been growing interest in synthetic polymer-based AMP mimics bearing both cationic and hydrophobic groups, which can be prepared through cost-effective polymerization processes. For example, simplified polymeric AMP analogs have been developed, including poly (methacrylamides) (31), poly(β-lactams) (14,(32)(33)(34)(35), polypeptides (36)(37)(38), poly(norborenes) (39,40), and poly(carbonates) (41,42). These compounds are considerably less expensive than peptides, and much work is being done to optimize them.…”

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confidence: 99%

Helical antimicrobial polypeptides with radial amphiphilicity

Xiong

Lee

Mansbach

et al. 2015

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

181

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α-Helical antimicrobial peptides (AMPs) generally have facially amphiphilic structures that may lead to undesired peptide interactions with blood proteins and self-aggregation due to exposed hydrophobic surfaces. Here we report the design of a class of cationic, helical homo-polypeptide antimicrobials with a hydrophobic internal helical core and a charged exterior shell, possessing unprecedented radial amphiphilicity. The radially amphiphilic structure enables the polypeptide to bind effectively to the negatively charged bacterial surface and exhibit high antimicrobial activity against both gram-positive and gram-negative bacteria. Moreover, the shielding of the hydrophobic core by the charged exterior shell decreases nonspecific interactions with eukaryotic cells, as evidenced by low hemolytic activity, and protects the polypeptide backbone from proteolytic degradation. The radially amphiphilic polypeptides can also be used as effective adjuvants, allowing improved permeation of commercial antibiotics in bacteria and enhanced antimicrobial activity by one to two orders of magnitude. Designing AMPs bearing this unprecedented, unique radially amphiphilic structure represents an alternative direction of AMP development; radially amphiphilic polypeptides may become a general platform for developing AMPs to treat drug-resistant bacteria.

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“…Zhou and co-workers used this method to prepare a series of random copolymers containing primary amines for lysine mimics and alkyl or aryl hydrophobic side chains as alanine, leucine or phenylalanine mimics. 53 The series investigated the optimum hydrophobic content for five different bacterial species (see previous section). The polymers synthesised by this method had narrow dispersities (1.11-1.28) and a range of molecular weights from 5kDa to 35kDa.…”

Section: Poly(carbonate)smentioning

confidence: 99%

Antimicrobial Polymers: Mimicking Amino Acid Functionali ty, Sequence Control and Three-dimensional Structure of Host-defen se Peptides

Hartlieb

Williams

Kuroki

et al. 2017

CMC

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(2017) Antimicrobial polymers : mimicking amino acid functionality, sequence control and threedimensional structure of host-defense peptides. Current Medicinal Chemistry, 24 . Permanent WRAP URL:http://wrap.warwick.ac.uk/88727 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. Publisher's statement:The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/149294/article A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. Abstract: Peptides and proteins control and direct all aspects of cellular function and communication.Having been honed by nature for millions of years, they also typically display an unsurpassed specificity for their biological targets. This underlies the continued focus on peptides as promising drug candidates. However, the development of peptides into viable drugs is hampered by their lack of chemical and pharmacokinetic stability and the cost of large scale production. One method to overcome such hindrances is to develop polymer systems that are able to retain the important structural features of these biologically active peptides, while being cheaper and easier to produce and manipulate chemically.This review illustrates these principles using examples of polymers designed to mimic antimicrobial host-defence peptides. The host-defence peptides have been identified as some of the most important leads for the next generation of antibiotics as they typically exhibit broad spectrum antimicrobial ability, low toxicity toward human cells and little susceptibility to currently known mechanisms of bacterial resistance. Their movement from the bench to clinic is yet to be realised, however, due to the limitations of these peptides as drugs. The literature provides a number of examples of polymers that have been able to mimic these peptides through all levels of structure, starting from specific amino acid sidechains, through to more global features such as overall charge, molecular weight and three-dimensional structure (e.g. α-helical). The resulting optimised polymers are able ret...

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High Potency and Broad-Spectrum Antimicrobial Peptides Synthesized via Ring-Opening Polymerization of α-Aminoacid-N-carboxyanhydrides

Cited by 154 publications

References 55 publications

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

Helical antimicrobial polypeptides with radial amphiphilicity

Antimicrobial Polymers: Mimicking Amino Acid Functionali ty, Sequence Control and Three-dimensional Structure of Host-defen se Peptides

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