Strategies in Translating the Therapeutic Potentials of Host Defense Peptides
The golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting...
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doaj-93d36010b0bf43adb4584d231ff490c22020-11-25T03:06:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00983538970Strategies in Translating the Therapeutic Potentials of Host Defense PeptidesDarren Shu Jeng Ting0Darren Shu Jeng Ting1Darren Shu Jeng Ting2Roger W. Beuerman3Harminder S. Dua4Harminder S. Dua5Rajamani Lakshminarayanan6Imran Mohammed7Larry A. Donoso Laboratory for Eye Research, Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United KingdomDepartment of Ophthalmology, Queen's Medical Centre, Nottingham, United KingdomAnti-infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore, SingaporeAnti-infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore, SingaporeLarry A. Donoso Laboratory for Eye Research, Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United KingdomDepartment of Ophthalmology, Queen's Medical Centre, Nottingham, United KingdomAnti-infectives Research Group, Singapore Eye Research Institute, The Academia, Singapore, SingaporeLarry A. Donoso Laboratory for Eye Research, Academic Ophthalmology, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United KingdomThe golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting AMR due to their rapid and unique antimicrobial action. Decades of research have advanced our understanding of the relationship between the physicochemical properties of HDPs and their underlying antimicrobial and non-antimicrobial functions, including immunomodulatory, anti-biofilm, and wound healing properties. However, the mission of translating novel HDP-derived molecules from bench to bedside has yet to be fully accomplished, primarily attributed to their intricate structure-activity relationship, toxicity, instability in host and microbial environment, lack of correlation between in vitro and in vivo efficacies, and dwindling interest from large pharmaceutical companies. Based on our previous experience and the expanding knowledge gleaned from the literature, this review aims to summarize the novel strategies that have been employed to enhance the antimicrobial efficacy, proteolytic stability, and cell selectivity, which are all crucial factors for bench-to-bedside translation of HDP-based treatment. Strategies such as residues substitution with natural and/or unnatural amino acids, hybridization, L-to-D heterochiral isomerization, C- and N-terminal modification, cyclization, incorporation with nanoparticles, and “smart design” using artificial intelligence technology, will be discussed. We also provide an overview of HDP-based treatment that are currently in the development pipeline.https://www.frontiersin.org/article/10.3389/fimmu.2020.00983/fullantibioticantimicrobial peptideantimicrobial resistanceartificial intelligencehost defense peptidenanoparticle |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Darren Shu Jeng Ting Darren Shu Jeng Ting Darren Shu Jeng Ting Roger W. Beuerman Harminder S. Dua Harminder S. Dua Rajamani Lakshminarayanan Imran Mohammed |
spellingShingle |
Darren Shu Jeng Ting Darren Shu Jeng Ting Darren Shu Jeng Ting Roger W. Beuerman Harminder S. Dua Harminder S. Dua Rajamani Lakshminarayanan Imran Mohammed Strategies in Translating the Therapeutic Potentials of Host Defense Peptides Frontiers in Immunology antibiotic antimicrobial peptide antimicrobial resistance artificial intelligence host defense peptide nanoparticle |
author_facet |
Darren Shu Jeng Ting Darren Shu Jeng Ting Darren Shu Jeng Ting Roger W. Beuerman Harminder S. Dua Harminder S. Dua Rajamani Lakshminarayanan Imran Mohammed |
author_sort |
Darren Shu Jeng Ting |
title |
Strategies in Translating the Therapeutic Potentials of Host Defense Peptides |
title_short |
Strategies in Translating the Therapeutic Potentials of Host Defense Peptides |
title_full |
Strategies in Translating the Therapeutic Potentials of Host Defense Peptides |
title_fullStr |
Strategies in Translating the Therapeutic Potentials of Host Defense Peptides |
title_full_unstemmed |
Strategies in Translating the Therapeutic Potentials of Host Defense Peptides |
title_sort |
strategies in translating the therapeutic potentials of host defense peptides |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-05-01 |
description |
The golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting AMR due to their rapid and unique antimicrobial action. Decades of research have advanced our understanding of the relationship between the physicochemical properties of HDPs and their underlying antimicrobial and non-antimicrobial functions, including immunomodulatory, anti-biofilm, and wound healing properties. However, the mission of translating novel HDP-derived molecules from bench to bedside has yet to be fully accomplished, primarily attributed to their intricate structure-activity relationship, toxicity, instability in host and microbial environment, lack of correlation between in vitro and in vivo efficacies, and dwindling interest from large pharmaceutical companies. Based on our previous experience and the expanding knowledge gleaned from the literature, this review aims to summarize the novel strategies that have been employed to enhance the antimicrobial efficacy, proteolytic stability, and cell selectivity, which are all crucial factors for bench-to-bedside translation of HDP-based treatment. Strategies such as residues substitution with natural and/or unnatural amino acids, hybridization, L-to-D heterochiral isomerization, C- and N-terminal modification, cyclization, incorporation with nanoparticles, and “smart design” using artificial intelligence technology, will be discussed. We also provide an overview of HDP-based treatment that are currently in the development pipeline. |
topic |
antibiotic antimicrobial peptide antimicrobial resistance artificial intelligence host defense peptide nanoparticle |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00983/full |
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