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

Abstract

(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...

Antimicrobial Susceptibility Testing of Antimicrobial Peptides to Better Predict Efficacy

“…For example, significant aggregation of the immunomodulatory AMP IDR-1018 occurred in the presence of phosphate, benzoate, nitrate, and citrate, but less aggregation was observed in the presence of acetate, chloride, water and, perhaps significantly, bicarbonate (see later). IDR-1018 also exhibited aggregation in 10% RPMI and 1% MEM tissue culture media and also co-precipitated with serum proteins in a concentration-dependent manner, in many cases adversely affected the desired immunomodulatory properties of the peptide and increased cytotoxicity (Hartlieb et al, 2017 ). Protegrin-4 (PG-4) also aggregates in the presence of phosphate (>2.0 mg/ml PG-4 in 50 mM sodium phosphate buffer, pH 7.4), forming amyloid-like fibrils and retained antimicrobial activity against B. subtilis (Gour et al, 2019 ).…”

Aggregation of Vibrio cholerae by Cationic Polymers Enhances Quorum Sensing but Overrides Biofilm Dissipation in Response to Autoinduction

“…Both natural and synthetic cationic macromolecules, such as cationic antimicrobial peptides, cationic polymers, and dendrimers, have been extensively reported as antimicrobial. 1 − 3 Because of their positive charge, these polymers can efficiently bind the negatively charged envelope of Gram-negative and Gram-positive bacteria. 4 − 6 At high concentrations and charge densities, these molecules have the potential to interfere with membrane integrity and decrease bacterial viability.…”

“… 4 − 6 At high concentrations and charge densities, these molecules have the potential to interfere with membrane integrity and decrease bacterial viability. 1 − 3 However, antimicrobial activity is heavily dependent on the length and nature of the polymer and, more importantly, on the nature of the targeted microbe. At low concentrations, cationic polymers are still capable of causing bacterial aggregation by mediating electrostatic interactions but do so without significantly affecting bacterial membrane integrity and growth.…”

The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides

“…Nevertheless, the use of HDPs is limited due to their low resistance to proteases, and their increased cost of preparation [ 8 , 13 , 14 ]. Different peptides [ 15 , 16 , 17 , 18 ], peptoids [ 19 , 20 , 21 , 22 , 23 ], polymethacrylate derivatives [ 24 ], polynorbornene derivatives [ 25 ], polycarbonate derivatives [ 26 ], peptide polymers [ 27 , 28 , 29 , 30 , 31 , 32 ], and polymers made by controlled living radical polymerization (CLRP) [ 33 ] were developed to mimic the antibacterial properties of HDPs, and to ameliorate their shortcomings [ 34 ].…”