Short, symmetric-helical peptides have narrow-spectrum activity with low resistance potential and high selectivity

Chou, Shuli; Wang, Jiajun; Shang, Lu; Akhtar, Muhammad Usman; Wang, Zhihua; Shi, Baoming; Feng, Xingjun; Shan, Anshan

doi:10.1039/c9bm00044e

Cited by 71 publications

(65 citation statements)

References 59 publications

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“…In this study, two symmetric heptad repeat sequences were connected by a short loop, and the sequence was designed as XXRXXRRzzRRXXRXX-NH 2 , where X represents Phe (F), Ile (I), and Leu (L), while zz represents Gly-Gly (GG) or d-Pro-Gly (pG). The net charge was +6 and the hydrophobicity was 40%-60%, which is consistent with the statistical information on natural AMPs [2,18]. Hydrophobic amino acids F, I, and L were used to damage microbial cell membranes [19].…”

Section: Introductionsupporting

confidence: 74%

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

Jia

Wang

Zhang

et al. 2020

IJMS

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Antimicrobial peptides (AMPs) have a unique action mechanism that can help to solve global problems in antibiotic resistance. However, their low therapeutic index and poor stability seriously hamper their development as therapeutic agents. In order to overcome these problems, we designed peptides based on the sequence template XXRXXRRzzRRXXRXX-NH 2 , where X represents a hydrophobic amino acid like Phe (F), Ile (I), and Leu (L), while zz represents Gly-Gly (GG) or d-Pro-Gly (pG). Showing effective antimicrobial activity against Gram-negative bacteria and low toxicity, designed peptides had a tendency to form an α-helical structure in membrane-mimetic environments. Among them, peptide LR pG (X: L, zz: pG) showed the highest geometric mean average treatment index (GM TI = 73.1), better salt, temperature and pH stability, and an additive effect with conventional antibiotics. Peptide LR pG played the role of anti-Gram-negative bacteria through destroying the cell membrane. In addition, peptide LR pG also exhibited an anti-inflammatory activity by effectively neutralizing endotoxin. Briefly, peptide LR pG has the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.

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Section: Introductionsupporting

confidence: 74%

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

Jia

Wang

Zhang

et al. 2020

IJMS

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“…Following this Trp motif, a positive-charged amino acid arginine (Arg), which causes toroidal pore defects in the anionic membrane and positively influences electrostatic interactions between peptides and the negatively charged bacterial membrane surface (Chou et al, 2016), was added to obtain amphipathic sequences. Our research indicated a vital role of the hydrophilic amino acid to adjust the antibacterial spectrum but its exact effect was not distinguished (Chou et al, 2019). Finally, the resulting primary peptide structure simplified as RRWyWWWyWRR, where y represents an uncharged hydrophilic amino acid (Schema 1) was proposed as a probiotic-neutral sequence.…”

Section: Introductionmentioning

confidence: 89%

“…The mechanism of the designed peptides was measured by fluorescence spectroscopy and electron microscopy as shown before. The fluorescent dyes disc 3 -5 , β-galactosidase, calcein and BC were used to determine cytoplasmic membrane depolarization and the binding affinities of the peptides to LPS and LTA (Wen et al, 2013;Chou et al, 2019). Briefly, for depolarization, 0.4 µM disc 3 -5 was added to the bacteria, which were washed and diluted into an OD600 of 0.05 with 5 mM HEPES buffers (containing 20 mM glucose and 0.1 KCl); for inner membrane permeability, bacteria incubated in LB containing 2% lactose were washed and diluted to an OD600 of 0.05 with 10 mM PBS (pH 7.4) containing 1.5 mM ONPG; for LPS or LTA binding, LPS/LTA and BC were mixed in Tris buffer (50 mM, pH 7.4) with a final concentration of 50 and 5 µg/ml, respectively.…”

Section: Antimicrobial Mechanism Measurementmentioning

confidence: 99%

“…And we tested the intracellular production of ROS by 2 , 7 -dichlorofluorescin diacetate (DCFH-DA) with bacteria of OD600 = 0.6 and DCFH-DA = 10 µM incubating for 1 h at 37 • C (Maurya et al, 2013;Lam et al, 2016). In addition, SEM, TEM, and CLSM were used to obtain direct visualization of bacterial membrane damage (Wang et al, 2018;Chou et al, 2019), and the bacteria samples (OD 600 = 0.05) were treated with 1 × MIC peptide for half an hour.…”

Section: Antimicrobial Mechanism Measurementmentioning

confidence: 99%

“…Female Institute for Cancer Research (ICR) mice (SPF, 20-25 g) were purchased from WeiTonglihua, Co., Ltd. (Beijing, China). Mice were fed and acclimatized as described (Chou et al, 2019). E. coli ATCC 25922 was adopted as the pathogenic bacterium for the infection model in this study.…”

Section: Mouse Model and Cytokine Assaymentioning

confidence: 99%

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Peptides With Triplet-Tryptophan-Pivot Promoted Pathogenic Bacteria Membrane Defects

Chou

Зайцева

et al. 2020

Front. Microbiol.

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Development of probiotic-ineffective antimicrobial peptides (AMPs)-based coatings that can kill pathogenic bacteria at low concentrations but are essentially harmless (even high concentrations) to probiotic organisms is a relatively new trend for therapy against GI tract infections. In this study, a series of triplet-tryptophan-pivot peptides with various hydrophilic amino acids was constructed. One AMP in particular, S7, showed bactericidal activity against Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli and antibiotic-resistant Staphylococcus aureus, yet was shown to be harmless to Lactobacillus rhamnosus, a key GI tract commensal. Furthermore, antibacterial mechanism assays, drug resistance assays, and mouse model tests suggested that S7 was useful in a clinical setting as it proved to significantly reduce bacterial load and cytokines (TNF-α, IL-6; P < 0.05) with a low probability of resistance via bacterial membrane physical destruction and formation of intracellular ROS. Combined, the results show that a triplet-tryptophan-pivot peptide containing a pair of serine residues was an excellent pathogen-selective candidate for medical devices and was potentially useful in food preservation, crop protection, and human health.

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Rational Design of Bio‐Inspired Peptide Electronic Materials toward Bionanotechnology: Strategies and Applications

Zhao,

Liu,

Tong

et al. 2024

Adv Funct Materials

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Biologically inspired peptide‐based materials, as novel charge transport materials, have gained increasing interest in bioelectronics due to their remarkable electrical properties and inherent biocompatibility. Extensive studies have shown that peptides can self‐assemble into a variety of hierarchical nanostructures with unique physical properties through supramolecular interactions. Therefore, peptide‐based materials hold great promise for applications in emerging electronic fields such as sensing, energy harvesting, energy storage, and electronic transmission. Herein, this work proposes a review article to summarize the rational design and research progress of peptide‐based materials and devices in bioelectronics. This work first introduces the design strategies and assembly mechanism for constructing high‐performance peptide‐based electronic materials and devices. In the following part, the applications of peptide‐based electronic materials and devices are systematically classified and discussed, including sensors, piezoelectric nanogenerators, electrodes, and semiconductors. Finally, the remaining challenges and future perspectives of peptide‐based bioelectronic materials and devices are presented. This work believes that this review will provide inspiration and guidance for the design and development of innovative peptide‐based smart materials in the field of bioelectronics.

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Short, symmetric-helical peptides have narrow-spectrum activity with low resistance potential and high selectivity

Abstract: A narrow-spectrum antimicrobial peptide was obtained via database-filtering technology and symmetric-structure; the peptide disturbed bacterial membrane and reduced the cytokine levels in serum in the mouse model.

Cited by 71 publications

References 59 publications

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

Peptides With Triplet-Tryptophan-Pivot Promoted Pathogenic Bacteria Membrane Defects

Rational Design of Bio‐Inspired Peptide Electronic Materials toward Bionanotechnology: Strategies and Applications

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