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Review
. 2018 Jan 19;8(1):4.
doi: 10.3390/biom8010004.

Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo

Prashant Kumar  1   2 , Jayachandran N Kizhakkedathu  3   4 , Suzana K Straus  5
Affiliations
Review

Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve the Activity and Biocompatibility In Vivo

Prashant Kumar et al. Biomolecules. .

Abstract

Antibiotic resistance is projected as one of the greatest threats to human health in the future and hence alternatives are being explored to combat resistance. Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads bacteria to develop no or low resistance. In this review, we discuss the diversity, history and the various mechanisms of action of AMPs. Although many AMPs have reached clinical trials, to date not many have been approved by the US Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage and short half-life. Some of the recent strategies developed to improve the activity and biocompatibility of AMPs, such as chemical modifications and the use of delivery systems, are also reviewed in this article.

Keywords: antimicrobial peptides; biocompatibility; bioconjugation; chemical modification; delivery systems; mechanism of action; proteolysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sources of antimicrobial peptides (total 2818) as of September 2017 from the antimicrobial peptide database. Numbers obtained from http://aps.unmc.edu/AP/, accessed on 20 September 2017.
Figure 2
Figure 2
Structural diversity of antimicrobial peptides (AMPs). (a) the α helical magainin, (b) β sheet human defensin 5 and (c) extended coil indolicidin. Positively charged residues are colored blue whereas hydrophobic residues are red. The N- and C-termini are indicated. The figure was generated using CHIMERA software [57,58,59].
Figure 3
Figure 3
Various mechanisms of action of antimicrobial peptides. Adapted with permission from [54]. MN: polymorphonuclear neutrophils; ADP: adenoside diphosphate; ATP: adenoside triphosphate.
Figure 4
Figure 4
Initial interaction of cationic AMPs with the multicellular animal (left) or bacterial (right) membrane. RBC: red blood cell.
Figure 5
Figure 5
Proposed mechanisms of action for AMPs in bacteria. See text for description of the various mechanisms and examples.
Figure 6
Figure 6
Structure of lipid II molecules with the pyrophosphate moiety circled in red.
Figure 7
Figure 7
Chemical modifications used to improve AMP properties: (a) use of d-amino acids such as lysine, (b) use of non-natural amino acids such as l-homoarginine, (c) various cyclization strategies, (d) use of a peptoid (1-dimensional structural difference relative to a peptide shown).
Figure 8
Figure 8
Various polymers used for AMP conjugation: (a) polyethylene glycol (PEG), (b) chitosan, (c) hyaluronic acid, (d) hyperbranched polyglycerol (HPG).
See this image and copyright information in PMC

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