Hartlieb, Matthias, Williams, E. G., Kuroki, Agnès, Perrier, Sébastien and Locock, K. E. (2017) Antimicrobial polymers : mimicking amino acid functionality, sequence control and three-dimensional structure of host-defense peptides. Current Medicinal Chemistry, 24 (19). pp. 2115-2140. doi:10.2174/0929867324666170116122322 ISSN 0929-8673.

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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 retain the activity profile of the peptides, but within a synthetic macromolecular construct that may be better suited to the development of a new generation of antimicrobial therapeutics. Such work has not only produced important new leads to combat the growing threat of antibiotic resistance, but may also open up new ways for polymers to mimic other important classes of biologically active peptides.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QR Microbiology R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Science, Engineering and Medicine > Science > Chemistry
Library of Congress Subject Headings (LCSH):	Peptide antibiotics, Polymers, Bacteria, Amino acids
Journal or Publication Title:	Current Medicinal Chemistry
Publisher:	Bentham Science Publishers Ltd.
ISSN:	0929-8673
Official Date:	16 January 2017
Dates:	Date Event 16 January 2017 Published 16 January 2017 Accepted
Volume:	24
Number:	19
Page Range:	pp. 2115-2140
DOI:	10.2174/0929867324666170116122322
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	30 May 2017
Date of first compliant Open Access:	16 January 2018
Funder:	Royal Society (Great Britain). Wolfson Research Merit Award (RSWRMA), Monash-Warwick Alliance, Deutsche Forschungsgemeinschaft (DFG), Commonwealth Scientific and Industrial Research Organization (Australia) (CSIRO)
Grant number:	WM130055 (RSWRMA), GZ: HA7725/1-1 (DFG)
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID WM130055 Royal Society UNSPECIFIED

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