The effect of structural modification of antimicrobial peptides on their antimicrobial activity, hemolytic activity, and plasma stability

ABSTRACT A class of antimicrobial peptides involved in host defense consists of sequences rich in Arg and Trp-R and -W. Analysis of the pharmacophore in these peptides revealed that chains as short as trimers of sequences such as WRW and RWR have antimicrobial activity (M. B. Strom, B. E. Haug, M. L. Skar, W. Stensen, T. Stiberg, and J. S. Svendsen, J. Med. Chem. 46:1567-1570, 2003). To evaluate the effect of chain length on antimicrobial activity, we synthesized a series of peptides containing simple sequence repeats, (RW) n -NH2 (where n equals 1, 2, 3, 4, or 5), and determined their antimicrobial and hemolytic activity. The antimicrobial activity of the peptides increases with chain length, as does the hemolysis of red blood cells. Within the experimental error, longer peptides (n equals 3, 4, or 5) show similar values for the ratio of hemolytic activity to antibacterial activity, or the hemolytic index. The (RW)3 represents the optimal chain length in terms of the efficacy of synthesis and selectivity as evaluated by the hemolytic index. Circular dichroism spectroscopy indicates that these short peptides appear to be unfolded in aqueous solution but acquire structure in the presence of phospholipids. Interaction of the peptides with model lipid vesicles was examined using tryptophan fluorescence. The (RW) n peptides preferentially interact with bilayers containing the negatively charged headgroup phosphatidylglycerol relative to those containing a zwitterionic headgroup, phosphatidylcholine.

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Novel Cathelicidin Antimicrobial Peptides from Paa robertingeri

Annual Research & Review in Biology ◽

10.9734/arrb/2019/v32i430093 ◽

2019 ◽

pp. 1-10

Author(s):

Qinghua Luo ◽

Huaiqing Deng ◽

Mengguang Yin ◽

Chen Chen ◽

Jiang Zhou

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Hemolytic Activity ◽

Fungal Species ◽

Human Erythrocytes ◽

Clinical Strain ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Novel Antibiotics

This study aimed to describe two cathelicidins (cathelicidin-PR1 and cathelicidin-PR2) from the skin of Paa robertingeri (Anura: Ranidae). The deduced mature peptides cathelicidin-PR1 and cathelicidin-PR2 were composed of 29 and 25 residues, respectively. Cathelicidin - PR1 has higher antimicrobial activity it could kill Gram-positive and Gram-negative bacteria and even some fungal species. Cathelicidin-PR1 exhibited more effective than AMP in antimicrobial activity against Pseydomonas maltophilia clinical strain. On the contrary, cathelicidin-PR2 had very weak antimicrobial activity. Furthermore, cathelicidin-PR1 and cathelicidin-PR2 exhibited very low hemolytic activity against human erythrocytes and little hemagglutinating activity. The results suggested that the cathelicidin-PR1 might serve as a template for developing novel antibiotics.

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Plant antimicrobial peptides: structures, functions, and applications

Botanical Studies ◽

10.1186/s40529-021-00312-x ◽

2021 ◽

Vol 62 (1) ◽

Author(s):

Junpeng Li ◽

Shuping Hu ◽

Wei Jian ◽

Chengjian Xie ◽

Xingyong Yang

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Agricultural Production ◽

Food Additives ◽

Antimicrobial Activities ◽

Gram Positive Bacteria ◽

Potential Applications ◽

Potential Applicability ◽

Bacteria And Fungi ◽

Positively Charged

AbstractAntimicrobial peptides (AMPs) are a class of short, usually positively charged polypeptides that exist in humans, animals, and plants. Considering the increasing number of drug-resistant pathogens, the antimicrobial activity of AMPs has attracted much attention. AMPs with broad-spectrum antimicrobial activity against many gram-positive bacteria, gram-negative bacteria, and fungi are an important defensive barrier against pathogens for many organisms. With continuing research, many other physiological functions of plant AMPs have been found in addition to their antimicrobial roles, such as regulating plant growth and development and treating many diseases with high efficacy. The potential applicability of plant AMPs in agricultural production, as food additives and disease treatments, has garnered much interest. This review focuses on the types of plant AMPs, their mechanisms of action, the parameters affecting the antimicrobial activities of AMPs, and their potential applications in agricultural production, the food industry, breeding industry, and medical field.

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Protein-Engineered Polymers Functionalized with Antimicrobial Peptides for the Development of Active Surfaces

Applied Sciences ◽

10.3390/app11125352 ◽

2021 ◽

Vol 11 (12) ◽

pp. 5352

Author(s):

Ana Margarida Pereira ◽

Diana Gomes ◽

André da Costa ◽

Simoni Campos Dias ◽

Margarida Casal ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Recombinant Dna ◽

Biological Properties ◽

Resistant Bacteria ◽

Recombinant Dna Technology ◽

Free Standing ◽

Microbial Cell Factories ◽

Cell Factories ◽

Antimicrobial Materials

Antibacterial resistance is a major worldwide threat due to the increasing number of infections caused by antibiotic-resistant bacteria with medical devices being a major source of these infections. This suggests the need for new antimicrobial biomaterial designs able to withstand the increasing pressure of antimicrobial resistance. Recombinant protein polymers (rPPs) are an emerging class of nature-inspired biopolymers with unique chemical, physical and biological properties. These polymers can be functionalized with antimicrobial molecules utilizing recombinant DNA technology and then produced in microbial cell factories. In this work, we report the functionalization of rPBPs based on elastin and silk-elastin with different antimicrobial peptides (AMPs). These polymers were produced in Escherichia coli, successfully purified by employing non-chromatographic processes, and used for the production of free-standing films. The antimicrobial activity of the materials was evaluated against Gram-positive and Gram-negative bacteria, and results showed that the polymers demonstrated antimicrobial activity, pointing out the potential of these biopolymers for the development of new advanced antimicrobial materials.

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Development of Antimicrobial Stapled Peptides Based on Magainin 2 Sequence

Molecules ◽

10.3390/molecules26020444 ◽

2021 ◽

Vol 26 (2) ◽

pp. 444

Author(s):

Motoharu Hirano ◽

Chihiro Saito ◽

Hidetomo Yokoo ◽

Chihiro Goto ◽

Ryuji Kawano ◽

...

Keyword(s):

Antimicrobial Activity ◽

Amino Acid ◽

Hemolytic Activity ◽

Helical Structure ◽

Antimicrobial Activities ◽

Side Chain ◽

Membrane Disruption ◽

Amino Acid Residues ◽

Electrophysiological Measurements ◽

Cell Membrane Disruption

Magainin 2 (Mag2), which was isolated from the skin of the African clawed frog, is a representative antimicrobial peptide (AMP) that exerts antimicrobial activity via microbial membrane disruption. It has been reported that the helicity and amphipathicity of Mag2 play important roles in its antimicrobial activity. We investigated and recently reported that 17 amino acid residues of Mag2 are required for its antimicrobial activity, and accordingly developed antimicrobial foldamers containing α,α-disubstituted amino acid residues. In this study, we further designed and synthesized a set of Mag2 derivatives bearing the hydrocarbon stapling side chain for helix stabilization. The preferred secondary structures, antimicrobial activities, and cell-membrane disruption activities of the synthesized peptides were evaluated. Our analyses revealed that hydrocarbon stapling strongly stabilized the helical structure of the peptides and enhanced their antimicrobial activity. Moreover, peptide 2 stapling between the first and fifth position from the N-terminus showed higher antimicrobial activity than that of Mag2 against both gram-positive and gram-negative bacteria without exerting significant hemolytic activity. To investigate the modes of action of tested peptides 2 and 8 in antimicrobial and hemolytic activity, electrophysiological measurements were performed.

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Rational design of novel amphipathic antimicrobial peptides focused on the distribution of cationic amino acid residues

MedChemComm ◽

10.1039/c9md00166b ◽

2019 ◽

Vol 10 (6) ◽

pp. 896-900 ◽

Cited By ~ 5

Author(s):

Takashi Misawa ◽

Chihiro Goto ◽

Norihito Shibata ◽

Motoharu Hirano ◽

Yutaka Kikuchi ◽

...

Keyword(s):

Antimicrobial Activity ◽

Amino Acid ◽

Human Cell ◽

Hemolytic Activity ◽

Rational Design ◽

Cell Cytotoxicity ◽

Amino Acid Residues ◽

High Antimicrobial Activity ◽

Cationic Amino Acid ◽

Helical Peptide

Amphipathic helical peptideStripeshowed high antimicrobial activity, low hemolytic activity, and low human cell cytotoxicity.

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The Design of Alapropoginine, a Novel Conjugated Ultrashort Antimicrobial Peptide with Potent Synergistic Antimicrobial Activity in Combination with Conventional Antibiotics

Antibiotics ◽

10.3390/antibiotics10060712 ◽

2021 ◽

Vol 10 (6) ◽

pp. 712

Author(s):

Ali Salama ◽

Ammar Almaaytah ◽

Rula M. Darwish

Keyword(s):

Antimicrobial Activity ◽

Hemolytic Activity ◽

Antimicrobial Agents ◽

Antimicrobial Activities ◽

Resistant Bacteria ◽

Human Red Blood Cells ◽

Drug Resistant Bacteria ◽

Different Strains ◽

Conventional Antibiotics

(1) Background: Antimicrobial resistance represents an urgent health dilemma facing the global human population. The development of novel antimicrobial agents is needed to face the rising number of resistant bacteria. Ultrashort antimicrobial peptides (USAMPs) are considered promising antimicrobial agents that meet the required criteria of novel antimicrobial drug development. (2) Methods: Alapropoginine was rationally designed by incorporating arginine (R), biphenylalanine (B), and naproxen to create an ultrashort hexapeptide. The antimicrobial activity of alapropoginine was evaluated against different strains of bacteria. The hemolytic activity of alapropoginine was also investigated against human erythrocytes. Finally, synergistic studies with antibiotics were performed using the checkerboard technique and the determination of the fractional inhibitory index. (3) Results: Alapropoginine displayed potent antimicrobial activities against reference and multi-drug-resistant bacteria with MIC values of as low as 28.6 µg/mL against methicillin-resistant S. aureus. Alapropoginine caused negligible toxicity toward human red blood cells. Moreover, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their antimicrobial concentrations. (4) Conclusions: The present study indicates that alapropoginine exhibits promising antimicrobial activity against reference and resistant strains of bacteria with negligible hemolytic activity. Additionally, the peptide displays synergistic or additive effects when combined with several antibiotics.

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Primary Structure Analysis of Antifungal Peptides from Cultivated and Wild Cereals

Plants ◽

10.3390/plants7030074 ◽

2018 ◽

Vol 7 (3) ◽

pp. 74 ◽

Cited By ~ 4

Author(s):

Eugene Rogozhin ◽

Dmitry Ryazantsev ◽

Alexey Smirnov ◽

Sergey Zavriev

Keyword(s):

Antimicrobial Activity ◽

Amino Acid ◽

Antifungal Activity ◽

Antimicrobial Peptides ◽

Structure Analysis ◽

Primary Structure ◽

Biologically Active ◽

Amino Acid Residues ◽

Wild Cereals ◽

Determining Factor

Cereal-derived bioactive peptides with antimicrobial activity have been poorly explored compared to those from dicotyledonous plants. Furthermore, there are a few reports addressing the structural differences between antimicrobial peptides (AMPs) from cultivated and wild cereals, which may shed light on significant varieties in the range and level of their antimicrobial activity. We performed a primary structure analysis of some antimicrobial peptides from wild and cultivated cereals to find out the features that are associated with the much higher antimicrobial resistance characteristic of wild plants. In this review, we identified and analyzed the main parameters determining significant antifungal activity. They relate to a high variability level in the sequences of C-terminal fragments and a high content of hydrophobic amino acid residues in the biologically active defensins in wild cereals, in contrast to AMPs from cultivated forms that usually exhibit weak, if any, activity. We analyzed the similarity of various physicochemical parameters between thionins and defensins. The presence of a high divergence on a fixed part of any polypeptide that is close to defensins could be a determining factor. For all of the currently known hevein-like peptides of cereals, we can say that the determining factor in this regard is the structure of the chitin-binding domain, and in particular, amino acid residues that are not directly involved in intermolecular interaction with chitin. The analysis of amino acid sequences of alpha-hairpinins (hairpin-like peptides) demonstrated much higher antifungal activity and more specificity of the peptides from wild cereals compared with those from wheat and corn, which may be associated with the presence of a mini cluster of positively charged amino acid residues. In addition, at least one hydrophobic residue may be responsible for binding to the components of fungal cell membranes.

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A Review of Antimicrobial Activity of Dental Mesenchymal Stromal Cells: Is There Any Potential?

Frontiers in Oral Health ◽

10.3389/froh.2021.832976 ◽

2022 ◽

Vol 2 ◽

Author(s):

Oleh Andrukhov ◽

Alice Blufstein ◽

Christian Behm

Keyword(s):

Vitamin D ◽

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Mesenchymal Stromal Cells ◽

Immune Cells ◽

Stromal Cells ◽

Multilineage Differentiation ◽

Differentiation Potential ◽

Health Maintenance ◽

Immunomodulatory Properties

Antimicrobial defense is an essential component of host-microbial homeostasis and contributes substantially to oral health maintenance. Dental mesenchymal stromal cells (MSCs) possess multilineage differentiation potential, immunomodulatory properties and play an important role in various processes like regeneration and disease progression. Recent studies show that dental MSCs might also be involved in antibacterial defense. This occurs by producing antimicrobial peptides or attracting professional phagocytic immune cells and modulating their activity. The production of antimicrobial peptides and immunomodulatory abilities of dental MSCs are enhanced by an inflammatory environment and influenced by vitamin D3. Antimicrobial peptides also have anti-inflammatory effects in dental MSCs and improve their differentiation potential. Augmentation of antibacterial efficiency of dental MSCs could broaden their clinical application in dentistry.

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