The Modification and Design of Antimicrobial Peptide

Gao, Yidan; Fang, Hengtong; Liu, Feng; Liu, Dawei; Liu, Jinsong; Su, Menghan; Fang, Zhi Yuan; Ren, Wenzhi; Jiao, Hailong

doi:10.2174/1381612824666180213130318

Cited by 37 publications

(32 citation statements)

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“…Therefore, AMPs are an ideal template for the development of new antimicrobials. Numerous studies have been devoted to improving the cell selectivity and antibacterial activity of AMPs [ 9 , 19 ]. Although the specific mechanism of action is unclear, moderate net positive charge and hydrophobicity are essential for the antimicrobial activity of AMPs [ 12 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Most natural AMPs are restricted in clinical applications due to their insufficient antimicrobial activity, high toxicity, and low stability [ 6 – 8 ]. Many strategies around positive polarity and hydrophobicity, including amino acid substitutions, cyclization, and fatty acid modification have been studied and adopted to overcome these disadvantages of AMPs [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification

et al. 2020

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Background The problem of increasing resistance against conventional antibiotics has drawn people’s attention. Therefore, the development of novel antibacterial agents with effective and safe therapeutic effects is imminent. Antimicrobial peptides (AMPs) are considered a promising class of antibacterial agents due to their broad antibacterial spectrum. Results In this study, on the basis of our previously studied peptide PMAP-37(F34-R), a novel antimicrobial peptide Chol-37(F34-R) was developed by N-terminal cholesterol modification to increase hydrophobicity. We observed that the N-terminal cholesterol-modified Chol-37(F34-R) showed higher antimicrobial activity than PMAP-37(F34-R) in vitro. Chol-37(F34-R) also exhibited effective anti-biofilm activity and may kill bacteria by improving the permeability of their membranes. Chol-37(F34-R) exerted high stability in different pH, salt, serum, and boiling water environments. Chol-37(F34-R) also showed no hemolytic activity and substantially low toxicity. Furthermore, Chol-37(F34-R) exhibited good potency of bacteria eradication and promoted wound healing and abscess reduction in infected mice. Meanwhile, in S. aureus ATCC25923-infected peritonitis model, Chol-37(F34-R) exhibited an impressive therapeutic effect by reducing the decrease in systemic bacterial burden and alleviating organ damage. Conclusions Our findings suggested that the N-terminal cholesterol modification of PMAP-37(F34-R) could improve antibacterial activity. Chol-37(F34-R) displayed excellent bactericidal efficacy and impressive therapeutic effect in vivo. Thus, Chol-37(F34-R) may be a candidate for antimicrobial agents against microbial infection in the clinic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification

et al. 2020

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“…Many current synthetic antimicrobial peptides used to treat human disease have been built around an existing scaffold from eukaryotes (Ashby, Petkova, & Hilpert, ). Novel AMP scaffolds identified through novel machine learning and minimal domain strategies can be subjected to further modification to refine their antimicrobial and cytotoxic properties (Gao et al, ). Our strategy to combine machine learning for de novo bacteriocin discovery along with biophysical refinement and minimal design represents a particularly robust workflow for the development of new antibiotic compounds.…”

Section: Discussionmentioning

confidence: 99%

Novel antimicrobial peptide discovery using machine learning and biophysical selection of minimal bacteriocin domains

Fields

Freed

Carothers

et al. 2019

Drug Development Research

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Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives. However, bacteriocins display diverse mechanisms of action, a narrow spectrum of activity, and inherent challenges in natural product isolation making in vitro verification of putative bacteriocins difficult. A subset of bacteriocins exert their antimicrobial effects through favorable biophysical interactions with the bacterial membrane mediated by the charge, hydrophobicity, and conformation of the peptide. We have developed a pipeline for bacteriocin‐derived compound design and testing that combines sequence‐free prediction of bacteriocins using machine learning and a simple biophysical trait filter to generate 20 amino acid peptides that can be synthesized and evaluated for activity. We generated 28,895 total 20‐mer candidate peptides and scored them for charge, α‐helicity, and hydrophobic moment. Of those, we selected 16 sequences for synthesis and evaluated their antimicrobial, cytotoxicity, and hemolytic activities. Peptides with the overall highest scores for our biophysical parameters exhibited significant antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. Our combined method incorporates machine learning and biophysical‐based minimal region determination to create an original approach to swiftly discover bacteriocin candidates amenable to rapid synthesis and evaluation for therapeutic use.

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“…Since most of the existing therapies have been rendered ineffective due to the rapid emergence and spread of resistance, AMPs act as precursor molecules for developing novel antimicrobial agents. Besides these advantages there are several limiting factors associated with the in-vivo use of AMPs such as susceptibility to proteolytic degradation, toxicity, poor bioavailability and expensive production at large scale [21] , [237] . Currently, considerable effort is being dedicated towards the synthesis of shorter and modified peptides with improved therapeutic efficacy, reduced cytotoxicity and decreased proteolytic digestion [237] , [238] .…”

Section: Future Roadmap and Conclusionmentioning

confidence: 99%

Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics

Sharma

Barman

Joshi

et al. 2022

Colloids and Surfaces B: Biointerfaces

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The decreasing effectiveness of conventional drugs due to multidrug-resistance is a major challenge for the scientific community, necessitating development of novel antimicrobial agents. In the present era of coronavirus 2 (COVID-19) pandemic, patients are being widely exposed to antimicrobial drugs and hence the problem of multidrug-resistance shall be aggravated in the days to come. Consequently, revisiting the phenomena of multidrug resistance leading to formulation of effective antimicrobial agents is the need of the hour. As a result, this review sheds light on the looming crisis of multidrug resistance in wake of the COVID-19 pandemic. It highlights the problem, significance and approaches for tackling microbial resistance with special emphasis on anti-microbial peptides as next-generation therapeutics against multidrug resistance associated diseases. Antimicrobial peptides exhibit exceptional mechanism of action enabling rapid killing of microbes at low concentration, antibiofilm activity, immunomodulatory properties along with a low tendency for resistance development providing them an edge over conventional antibiotics. The review is unique as it discusses the mode of action, pharmacodynamic properties and application of antimicrobial peptides in areas ranging from therapeutics to agriculture.

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The Modification and Design of Antimicrobial Peptide

Cited by 37 publications

References 0 publications

Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification

Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification

Novel antimicrobial peptide discovery using machine learning and biophysical selection of minimal bacteriocin domains

Multidrug resistance crisis during COVID-19 pandemic: Role of anti-microbial peptides as next-generation therapeutics

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