Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa

Kim, Hyun; Jang, Ju Hye; Kim, Sun Chang; Cho, Ju Hyun

doi:10.1016/j.ejmech.2019.111814

Cited by 53 publications

(42 citation statements)

References 40 publications

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“…The conjugation of different AMPs can also be performed. For example, the hybrid peptide (PA2-GNU7) constructed by the addition of PA2 to GNU7 has a high activity and specificity to P. aeruginosa (Kim et al, 2020).…”

Section: Conjugationmentioning

confidence: 99%

“…Hybrid peptides have also been used to build targeting peptides. For example, PA2, which is a P. aeruginosa-targeting peptide, was combined with GNU7 (a broad-spectrum AMP) to construct a hybrid peptide (PA2-GNU7) that targets OprF protein and has good bactericidal activity and specificity (Kim et al, 2020). Furthermore, some antibiotics, for instance, daptomycin (a lipopeptide), lugdunin which is a 21-membered cyclic peptide consists of 6 amino acid residues plus a thiazolidine moiety and telavancin (a glycopeptide) have been widely used for the clinic (Durand et al, 2019;Lampejo, 2020).…”

Section: Current Progress and Application Of Antimicrobial Peptides Mmentioning

confidence: 99%

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Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

et al. 2020

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Antimicrobial peptides (AMPs) are a class of small peptides that widely exist in nature and they are an important part of the innate immune system of different organisms. AMPs have a wide range of inhibitory effects against bacteria, fungi, parasites and viruses. The emergence of antibiotic-resistant microorganisms and the increasing of concerns about the use of antibiotics resulted in the development of AMPs, which have a good application prospect in medicine, food, animal husbandry, agriculture and aquaculture. This review introduces the progress of research on AMPs comprehensively and systematically, including their classification, mechanism of action, design methods, environmental factors affecting their activity, application status, prospects in various fields and problems to be solved. The research progress on antivirus peptides, especially anti-coronavirus (COVID-19) peptides, has been introduced given the COVID-19 pandemic worldwide in 2020.

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Section: Conjugationmentioning

confidence: 99%

Section: Current Progress and Application Of Antimicrobial Peptides Mmentioning

confidence: 99%

Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

et al. 2020

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“…Although resistance occurs naturally, the overuse and misuse of broad-spectrum antibiotics has accelerated the increase in resistance [3]. Therefore, to avoid unintentional elicitation of antibiotic resistance or disruption of microbiota, the use of a species-selective antimicrobial agent, which specifically targets and kills the disease-causing strain, has been suggested [4][5][6]. However, no new class of antibiotics has been developed for infections triggered by Gram-negative bacteria, including P. aeruginosa, in the last 40 years; in addition, 2 of 31 most of the antibiotics in late-stage clinical development belong to existing classes of drugs against which bacterial resistance has already been observed or could easily develop [7,8].…”

Section: Introductionmentioning

confidence: 99%

Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

et al. 2021

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Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a–d, pyridine-2-one 3–10, and 2-imino-2H-chromene-3-carboxamide 11, 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis. All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens. The most promising six derivatives, 2a, 2b, 2d, 3a, 8, and 11, revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity. These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives 2d, 3a, and 2a demonstrating inhibition of DNA gyrase, with IC50 values of 18.17–23.87 µM, and of DHFR, with IC50 values of 4.33–5.54 µM; their potency is near to that of the positive controls. Further, the six derivatives exhibited immunomodulatory potential and three derivatives, 2d, 8, and 11, were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4+ and CD8+ T lymphocytes. Finally, molecular docking and some AMED studies were performed.

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“…In addition to overcoming the issue of host toxicity (as described above), the hybrid strategy has also led to the development of numerous species-specific and targeted bactericidal peptides to prevent damage to useful microbiome (122)(123)(124). Kim et al (122) have developed a targeted chimeric peptide for the treatment of P. aeruginosa infection.…”

Section: Hybridizationmentioning

confidence: 99%

Strategies in Translating the Therapeutic Potentials of Host Defense Peptides

et al. 2020

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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.

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Development of a novel hybrid antimicrobial peptide for targeted killing of Pseudomonas aeruginosa

Cited by 53 publications

References 40 publications

Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields

Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

Strategies in Translating the Therapeutic Potentials of Host Defense Peptides

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