Computational Peptide Engineering Approach for Selection the Best Engendered Camel Lactoferrin-Derive Peptide with Potency to Interact with DNA

Pirkhezranian, Zana; Tahmoorespur, Mojtaba; Monhemi, Hassan; Sekhavati, Mohammad Hadi

doi:10.1007/s10989-019-10012-7

Cited by 7 publications

(3 citation statements)

References 38 publications

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“…in vitro antibacterial, anti-biofilm and antioxidant activity of the recombinant chimeric peptide were determined on some food spoilage bacterial strains. Finally, using computational modeling approaches we try to predict peptide interaction to lipopolysaccharides (LPS) and DNA as two main targets in bacteria [15,36,50,51].…”

Section: Introductionmentioning

confidence: 99%

Generation of an engineered food-grade Lactococcus lactis strain for production of an antimicrobial peptide: in vitro and in silico evaluation

et al. 2020

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Background: Foodborne pathogens and their biofilms are considered as one of the most serious problems in human health and food industry. Moreover, safety of foods is a main global concern because of the increasing use of chemical food additives. Ensuring food safety enhances interest in discovery of new alternative compounds such as antimicrobial peptides (AMPs), which can be used as bio-preservatives in the food industry. In this study, the most important antimicrobial peptides of camel milk lactoferrin (lactoferrampin and lactoferricin) were recombinantly expressed in the form of chimeric peptide (cLFchimera) in a food-grade L. lactis strain. P170 expression system was used to express secreted cLFchimera using pAMJ1653 expression vector which harbors a safe (non-antibiotic) selectable marker. Results: Peptide purification was carried out using Ni-NTA agarose column from culture medium with concentration of 0.13 mg/mL. The results of disk diffusion test revealed that cLFchimera had considerable antimicrobial activity against a number of major foodborne bacteria. Furthermore, this chimeric peptide showed strong and weak inhibitory effect on biofilm formation against P. aeruginosa, S. aureus E. faecalis, and E. coli, respectively. Antioxidant activity and thermal stability of the chimeric peptide was determined. The results showed that cLFchimera had antioxidant activity (IC 50 : 310 μ/mL) and its activity was not affected after 40 min of boiling. Finally, we evaluated the interaction of the peptide with LPS and DNA in bacteria using molecular dynamic simulation as two main intra and extra cellular targets for AMPs, respectively. Our in silico analysis showed that cLFchimera had strong affinity to both of these targets by positive charged residues after 50 ns molecular dynamic simulation. Conclusions: Overall, the engineered food-grade L. lactis generated in the present study successfully expressed a secreted chimeric peptide with antimicrobial properties and could be considered as a promising bio-preservative in the food industry.

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Section: Introductionmentioning

confidence: 99%

Generation of an engineered food-grade Lactococcus lactis strain for production of an antimicrobial peptide: in vitro and in silico evaluation

et al. 2020

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“…In this regards, Reyes-Cortes et al, (2017) showed that this chimeric peptide mediated its antibacterial activity by entering the cytoplasm through translocation across the bacterial membrane and possibly interacting with internal organelles [33]. Consistent with these results, Pirkhezranian et al, (2020 a, b) using molecular simulation analysis showed that cLFchimera and its derivatives had a higher a nity for DNA interaction and hypothesized this chimeric peptide mediated its activity by intramolecular mechanisms which interference DNA related pathways such as DNA replication [34,35]. However, treatment of all bacteria with antibiotics and their combinations (antibiotics + peptide) resulted signi cantly increased the release of cellular contents.…”

Section: Discussionmentioning

confidence: 83%

Antibacterial Activity of cLFchimera and its Synergistic Potential with Antibiotics against Some Foodborne Pathogens Bacteria

Roshanak

Pirkhezranian

Shahidi

et al. 2020

Preprint

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Background: Frequent and unlimited use of antibiotics caused the development of antibiotic resistance by microorganisms. Therefore, there is an argent need to discover novel antibacterial agents or a combination of agents as a safe treatment strategy for various infections. The aim of the present study was to evaluate the synergistic effects of cLFchimera, an antimicrobial peptides (AMPs), and antibiotics on several foodborne bacterial strains. Methods: A checkerboard method was used to determine the synergistic effects of cLFchimera and several antibiotics (Gentamicin, Cefazolin and Ceftazidime) on bacterial strains (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi). Results: The combination of cLFchimera and antibiotics generated a total and partial synergistic interaction for all foodborne bacterial strain used in the present study (FIC= 0.25 to 0.77). In most cases, the effect of peptide and antibiotic synergist on release of cellular content was not different compared to antibiotics when they used alone, but the count of viable cells significantly decreased in combination peptide and antibiotics treatments. Generally, antibacterial dynamics of the combination of peptide and antibiotics showed an increase and stable trend after reaching the peak point for E. coli, P. aeruginosa and S. typhi, respectively. Scanning electron microscopy analysis showed that bacterial cells treated with the combination Gentamycin and cLFchimera were markedly damaged, and most of the outermost layer of the bacterial cells disappeared. Conclusion: Overall, our results may suggest that cLFchimera mediated its synergistic activity independent to antibiotics mode of action by disrupting the cell membrane and intramolecular mechanisms.

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“…[ 7 ] Rational design of peptide drugs has received growing attention as a result of the low experimental costs. [ 8 , 9 ] The development of structural biology has led to the discovery of protein or peptide drugs entering a new era. [ 10 , 11 ] Designing peptide drugs is a top-down process, the first step is to build a peptide library, followed by peptide docking to the receptor to filter strong binding peptides.…”

Section: Introductionmentioning

confidence: 99%

Discovering peptide inhibitors of thrombin as a strategy for anticoagulation

Zhen,

Wang,

et al. 2024

Medicine

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Unusual blood clots can cause serious health problems, such as lung embolism, stroke, and heart attack. Inhibiting thrombin activity was adopted as an effective strategy for preventing blood clots. In this study, we explored computational-based method for designing peptide inhibitors of human thrombin therapeutic peptides to prevent platelet aggregation. The random peptides and their 3-dimentional structures were generated to build a virtual peptide library. The generated peptides were docked into the binding pocket of human thrombin. The designed strong binding peptides were aligned with the native binder by comparative study, and we showed the top 5 peptide binders display strong binding affinity against human thrombin. The 5 peptides were synthesized and validated their inhibitory activity. Our result showed the 5-mer peptide AEGYA, EVVNQ, and FASRW with inhibitory activity against thrombin, range from 0.53 to 4.35 μM. In vitro anti-platelet aggregation assay was carried out, suggesting the 3 peptides can inhibit the platelet aggregation induced by thrombin. This study showed computer-aided peptide inhibitor design can be a robust method for finding potential binders for thrombin, which provided solutions for anticoagulation.

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Computational Peptide Engineering Approach for Selection the Best Engendered Camel Lactoferrin-Derive Peptide with Potency to Interact with DNA

Cited by 7 publications

References 38 publications

Generation of an engineered food-grade Lactococcus lactis strain for production of an antimicrobial peptide: in vitro and in silico evaluation

Generation of an engineered food-grade Lactococcus lactis strain for production of an antimicrobial peptide: in vitro and in silico evaluation

Antibacterial Activity of cLFchimera and its Synergistic Potential with Antibiotics against Some Foodborne Pathogens Bacteria

Discovering peptide inhibitors of thrombin as a strategy for anticoagulation

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