A Review of Antimicrobial Peptides and Their Therapeutic Potential as Anti-Infective Drugs

Gordon, Y. Jerold; Romanowski, Eric G.; McDermott, Alison M.

doi:10.1080/02713680590968637

Cited by 612 publications

(516 citation statements)

References 60 publications

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“…Gabriel et al [70] concluded that only N-terminal conjugation permitted the appropriate parallel orientation of the peptide helices, which is required for interaction among the peptide molecules and between the peptides and the lipid double layer during membrane pore formation. These results are supported by the reported key role of basic lysine side-chains (and of those from other basic amino acids, as arginine or histidine) in the bioactivity of cationic AMP [39][40][41][42], which could explain the deleterious effect of AMP immobilization through Lys e-amino groups towards antimicrobial activity. The possibility of C-terminal peptide immobilization should be considered as this orientation may achieve similar specific activity as N-terminal conjugation.…”

Section: Peptide Orientation After Immobilizationsupporting

confidence: 65%

“…There is a clear need for a broad-spectrum antimicrobial that prevents colonization of biomaterials, minimizes the development of bacterial resistance, displays long-term stability, even through the sterilization process, and has a low cytotoxic profile. Antimicrobial peptides have the potential to meet these criteria [39][40][41][42] and therefore represent a promise for the new generation of antimicrobial surfaces.…”

Section: Antimicrobial Coatingsmentioning

confidence: 99%

“…The decline in the effectiveness of current therapies has led to a search for new kinds of agents, including antibiotics based on antimicrobial peptides (AMPs), which are part of the innate immune system of all multicellular organisms [39][40][41][42][43]. So far, more than 750 different AMPs have been isolated from a wide variety of animals, plants, bacteria, fungi and viruses [39][40][41][42]44]. The AMPs comprise a chemically and structurally heterogeneous family.…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

“…Uncontrolled immobilization can be especially detrimental when involving peptide amine groups, as these amine groups are normally provided by lysines which are key amino acids in the majority of cationic amphipathic AMPs [39][40][41][42].…”

Section: Solid Supports and Chemical Coupling Strategiesmentioning

confidence: 99%

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Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces

et al. 2011

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a b s t r a c tBacterial adhesion to biomaterials remains a major problem in the medical devices field. Antimicrobial peptides (AMPs) are well-known components of the innate immune system that can be applied to overcome biofilm-associated infections. Their relevance has been increasing as a practical alternative to conventional antibiotics, which are declining in effectiveness. The recent interest focused on these peptides can be explained by a group of special features, including a wide spectrum of activity, high efficacy at very low concentrations, target specificity, anti-endotoxin activity, synergistic action with classical antibiotics, and low propensity for developing resistance. Therefore, the development of an antimicrobial coating with such properties would be worthwhile. The immobilization of AMPs onto a biomaterial surface has further advantages as it also helps to circumvent AMPs' potential limitations, such as short half-life and cytotoxicity associated with higher concentrations of soluble peptides. The studies discussed in the current review report on the impact of covalent immobilization of AMPs onto surfaces through different chemical coupling strategies, length of spacers, and peptide orientation and concentration. The overall results suggest that immobilized AMPs may be effective in the prevention of biofilm formation by reduction of microorganism survival post-contact with the coated biomaterial. Minimal cytotoxicity and longterm stability profiles were obtained by optimizing immobilization parameters, indicating a promising potential for the use of immobilized AMPs in clinical applications. On the other hand, the effects of tethering on mechanisms of action of AMPs have not yet been fully elucidated. Therefore, further studies are recommended to explore the real potential of immobilized AMPs in health applications as antimicrobial coatings of medical devices.

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Section: Peptide Orientation After Immobilizationsupporting

confidence: 65%

Section: Antimicrobial Coatingsmentioning

confidence: 99%

Section: Antimicrobial Peptidesmentioning

confidence: 99%

Section: Solid Supports and Chemical Coupling Strategiesmentioning

confidence: 99%

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Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces

et al. 2011

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“…The reasons for peptide "failure" at Phase III clinical trials and non-progression to product registration include lack of efficacy, non-superiority over standard care antibiotics and safety and it should be noted that the underlying reasons for these clinical outcomes have not been reported. 107 We speculate that early attempts to deliver new therapies, and in particular peptides, were hampered by lack of investment, use of non-optimised peptides and insufficient development and clinical expertise.…”

Section: The Portfolio Of Alternative Approachesmentioning

confidence: 99%

Alternatives to antibiotics—a pipeline portfolio review

Czaplewski¹,

Bax²,

Clokie

et al. 2016

The Lancet Infectious Diseases

726

530

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For 70 years antibiotics have saved countless lives and enabled the development of modern medicine, but it is becoming clear that the success of antibiotics may have only been temporary and we now anticipate a long-term, generational and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. As the search for new conventional antibiotics has become less productive and there are no clear strategies to improve success, a broader approach to address bacterial infection is needed. This review of potential alternatives to antibiotics (A2As) was commissioned by the Wellcome Trust, jointly funded by the Department of Health, and involved scientists and physicians from academia and industry. For the purpose of this review, A2As were defined as non-compound approaches (that is, products other than classical antibacterial agents) that target bacteria or approaches that target the host. In addition, the review was limited to agents that had potential to be administered orally, by inhalation or by injection for treatment of systemic/invasive infection. Within these criteria, the review has identified 19 A2A approaches now being actively progressed. The feasibility and potential clinical impact of each approach was considered. The most advanced approaches (and the only ones likely to deliver new treatments by 2025) are antibodies, probiotics, and vaccines now in Phase II and Phase III trials. These new agents will target infections caused by P. aeruginosa, C. difficile and S. aureus. However, other than probiotics for C. difficile, this first wave will likely best serve as adjunctive or preventive therapies. This suggests that conventional antibiotics will still be needed. The economics of pathogen-specific therapies must improve to encourage innovation, and greater investment into A2As with broad-spectrum activity (e.g. antimicrobial-, host defense-and, anti-biofilm peptides) is needed. Increased funding, estimated at >£1.5 bn over 10 years is required to validate and then develop these A2As. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches at Clinical Phase II proof of concept. Such an approach could transform our understanding of A2As as effective new therapies and should provide the catalyst required for both active engagement and investment by the pharma/biotech industry. Only a sustained, concerted and coordinated international effort will provide the solutions needed for the next decade.

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Membrane‐Targeted Enzybiotics

Gasset

2009

Enzybiotics

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A Review of Antimicrobial Peptides and Their Therapeutic Potential as Anti-Infective Drugs

Abstract: While AMPs are recognized as essential components of natural host innate immunity against microbial challenge, their usefulness as a new class of antimicrobial drugs still remains to be proven.

Cited by 612 publications

References 60 publications

Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces

Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces

Alternatives to antibiotics—a pipeline portfolio review

Membrane‐Targeted Enzybiotics

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