Development of a novel antimicrobial peptide AWRK6

Kim, Dusik; Wang, Zheng; Jin, Lili; Li, Hanpin; Hwang, Junwei; Hanrahan, John W.; Wang, Qiuyu

doi:10.3329/bjp.v11i2.25031

Cited by 8 publications

(12 citation statements)

References 24 publications

(31 reference statements)

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“…This peptide was used to generate the cationic homologue, AWRK6, by the substitution of lysine residues for each of the six arginines possessed by Dy2, as well as the substitution of tryptophan residue for alanine at position 2 of Dy2 (Table 2). In the case of both peptides, alkaline pH promoted increased levels of α-helical structure in the presence of membranes that correlated with enhanced antibacterial activity 265 . Previous studies have shown that pH induced increases in the α-helicity of AMPs can enhance their amphiphilicity and / or hydrophobicity, thereby facilitating higher levels of membranolytic action 37 .…”

Section: Amps From Amphibiansmentioning

confidence: 93%

Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications

Phoenix

Harris

Dennison

2021

CPPS

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: A number of disorders and diseases are associated with conditions of high pH and many conventional antibiotics lose their efficacy under these pH conditions, generating a need for novel antimicrobials, and a potential solution to fulfil this need is antimicrobial peptides (AMPs) with high pH optima. This review shows that a variety of anionic and cationic AMPs with this pH dependency are produced by creatures across the eukaryotic kingdom, including humans, rabbits, cattle, sheep, fish and frogs. These AMPs exhibit activity against viruses, bacteria and fungi that involves membrane interactions and appear to be facilitated by a variety of mechanisms that generally promote passage across membranes to attack intracellular targets, such as DNA or protein synthesis, and / or membrane lysis. Some of these mechanisms are unknown but those elucidated include the use of bacterial pores and transporters, the self-promoted uptake pathway and established models of membrane interaction, such as the carpet mechanism, toroidal pore formation, the adoption of tilted peptide and the SHM model. A variety of potential roles have been proposed for these AMPs, including use as antivirals, antibacterials, antifungals, adjuvants to antimicrobial therapy, biomarkers of disease and probes for pathogenic microbes. In this review, these properties are described and discussed, with an emphasis on the antimicrobial mechanisms used by these AMPs and the pH dependency of these mechanisms.

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Section: Amps From Amphibiansmentioning

confidence: 93%

Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications

Phoenix

Harris

Dennison

2021

CPPS

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“…Replacement of the Arg residues originally present in dybowskin-2CDYa with Lys residues resulted in higher affinity to anionic liposomes than to zwitterionic ones. Studies of antimicrobial activity indicated that AWRK6 was more active against Gram-positive than Gram-negative bacteria, and was 2–4-fold more potent compared to dybowskin-2CDYa, being found to be at the level of 4–8 μg/mL against S. aureus and 32 μg/mL against E. coli [ 13 ].…”

Section: De Novo Designed Antimicrobial Immunomodulatory Peptidesmentioning

confidence: 99%

Synthetic Antimicrobial Immunomodulatory Peptides: Ongoing Studies and Clinical Trials

Lesiuk¹,

Paduszynska

Greber

2022

Antibiotics

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The increasingly widespread antimicrobial resistance forces the search for new antimicrobial substances capable of fighting infection. Antimicrobial peptides (AMPs) and their synthetic analogs form an extensive group of compounds of great structural diversity and multifunctionality, different modes of antimicrobial action, and considerable market potential. Some AMPs, in addition to their proven antibacterial, antifungal, and antiviral activity, also demonstrate anti-inflammatory and immunomodulatory capabilities; these are called innate defense regulator (IDR) peptides. IDR peptides stimulate or inhibit the body’s immune system, e.g., by stimulating leukocyte migration to the site of infection, driving macrophage differentiation and activation, providing chemotactic action for neutrophils, degranulation and activation of mast cells, altering chemokine and cytokine production, and even induction of angiogenesis and wound healing. Such multifunctional immunomodulatory peptide molecules are currently being investigated and developed. Exploring and utilizing IDR peptides as an indirect weapon against infectious diseases could represent a completely new strategy to cope with the issue of antimicrobial resistance.

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“…Amphibian skin secretions are a rich source of bioactive peptides [ 1 , 5 ]. In our previous study, a series of novel peptides were discovered in frog ( Rana dybowskii ) skin, and dybowskin-2CDYa was later modified to improve the stability, acquiring a novel peptide, namely AWRK6 [ 6 , 7 ]. AWRK6 presented antibacterial and lipopolysaccharide-neutralizing activities, and it has been discovered that AWRK6 regulates glycolipid metabolism to improve type 2 diabetes mellitus and metabolic associated fatty liver disease (MAFLD) [ 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Determination of the Peptide AWRK6 in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and Its Application to Pharmacokinetics

et al. 2021

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AWRK6 was a synthesized peptide developed based on the natural occurring peptide dybowskin-2CDYa, which was discovered in frog skin in our previous study. Here, a quantitative determination method for AWRK6 analysis in rat plasma by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and validated following U.S. FDA guidelines. A combination of plasma precipitation and liquid–liquid extraction was applied for the extraction. For pharmacokinetics study, the rats were administrated with AWRK6 via intraperitoneal and intravenous injection. The prepared plasma samples were separated on an ODS column and analyzed by tandem MS using precursor-to-product ion pairs of m/z: 533.4→84.2 for AWRK6 and m/z: 401.9→101.1 for internal standard Polymyxin B sulfate in multiple reaction monitoring mode. AWRK6 concentrations in rat plasma peaked at about 1.2 h after intraperitoneal injections at 2.35, 4.7 and 9.4 mg/kg bodyweight. The terminal half-life was around 2.8 h. The absolute bioavailability of AWRK6 was 50% after 3 doses via injection, and the apparent volume of distribution was 4.884 ± 1.736 L. The obtained determination method and pharmacokinetics profiles of AWRK6 provides a basis for further development, and forms a benchmark reference for peptide quantification.

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Development of a novel antimicrobial peptide AWRK6

Cited by 8 publications

References 24 publications

Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications

Antimicrobial Peptides with pH-Dependent Activity and Alkaline Optima: Their Origins, Mechanisms of Action and Potential Applications

Synthetic Antimicrobial Immunomodulatory Peptides: Ongoing Studies and Clinical Trials

Determination of the Peptide AWRK6 in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and Its Application to Pharmacokinetics

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