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  • Review Article
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Synthetic peptide branched polymers for antibacterial and biomedical applications

Nature Reviews Bioengineering volume 2, pages 343–361 (2024)Cite this article

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Abstract

Antimicrobial resistance is a major threat to human health, and this ‘invisible pandemic’ is a looming public health crisis. Accordingly, both broad-spectrum and selective antimicrobial agents that do not induce resistance are urgently required. Synthetic peptide-polymers and their mimics and in particular structurally nano-engineered antimicrobial peptide-polymers (SNAPPs) are antimicrobial materials with clinical potential as novel therapeutics to combat antimicrobial resistance due to their inherent biodegradability, biocompatibility and tuneable cytocompatibility. Macromolecular design in conjunction with rational monomer composition can direct their architecture, self-assembly and chemical behaviour, ultimately guiding the choice of appropriate application within the biomedical field. This Review focuses on several facets of antimicrobial peptide-polymers including their synthesis, diversity, physicochemical properties and bacteria-killing mechanisms. We discuss current strategies in the antimicrobial field that improve antibacterial activity in the context of their current and potential application to peptide-polymers. Further, different strategies to enhance the antibacterial activity of peptide-polymers are discussed, along with burgeoning developments in medical applications. The challenges of future applications of synthetic peptide branched polymers in biomedical engineering are highlighted.

Key points

  • Infectious diseases caused by antibiotic-resistant pathogens are one of the greatest challenges to global health care.

  • Synthetic peptide branched polymers produced by ring-opening polymerization of N-carboxyanhydride amino acids have exquisite antimicrobial efficacy while maintaining the peptide-polymer advantages of being highly biocompatible, biodegradable materials with highly potent antimicrobial activity.

  • Structurally nano-engineered antimicrobial peptide-polymers (SNAPPs) are an example of these synthetic peptide branched polymers.

  • SNAPPs, and other peptide-polymers, possess multiple mechanisms of action for killing bacteria, which reduces the ability of bacteria to develop resistance.

  • Peptide-polymers have unique synthesis advantages as their production is more cost-effective than antimicrobial peptides made by solid-phase peptide synthesis. They can also be made on a large scale and can incorporate a variety of post-modifications.

  • Synthetic peptide branched polymers might be used for drug delivery, gene therapy, tissue engineering, vaccine therapeutics and other biomedical applications.

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Fig. 1: Synthetic peptide branched polymers.
Fig. 2: Schematic representation of the potential secondary structure of individual SNAPP arms.
Fig. 3: Mechanisms of antimicrobial action of antimicrobial peptides and SNAPPs.
Fig. 4: Chemical modification of SNAPPs and other polymers.
Fig. 5: Schematic showing the broad range of applications of synthetic peptide branched polymers.

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Acknowledgements

G.G.Q. and N.M.O’B.-S. acknowledge funding support from The National Health and Medical Research Council (NHMRC) of Australia (APP1142472, APP1158841 and APP1185426) and the Australian Research Council (ARC) (DP210102781 and DP160101312).

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Authors and Affiliations

  1. Polymer Science Group, Department of Chemical Engineering, The University of Melbourne, Melbourne, Victoria, Australia

    Sadegh Shabani & Greg G. Qiao

  2. ACTV Research group, Melbourne Dental School, Division of Basic and Clinical Oral Sciences, Royal Dental Hospital and The Bio21 Institute of Molecular Science and Biotechnology, The University of Melbourne, Melbourne, Victoria, Australia

    Sara Hadjigol, Wenyi Li & Neil M. O’Brien-Simpson

  3. Nanyang Technological University, Singapore, Singapore

    Zhangyong Si & Mary B. Chan-Park

  4. Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore

    Dicky Pranantyo

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S.S., S.H., W.L., Z.S. and D.P. researched data for the article, made a substantial contribution to discussion of content and wrote the article. M.B.C.-P., G.G.Q. and N.M.O’B.-S. made a substantial contribution to discussion of content, wrote and reviewed/edited the manuscript before submission.

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Shabani, S., Hadjigol, S., Li, W. et al. Synthetic peptide branched polymers for antibacterial and biomedical applications. Nat Rev Bioeng 2, 343–361 (2024). https://doi.org/10.1038/s44222-023-00143-4

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