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

Wang, Taoran; Zou, Cunbin; Na, Wen; Liu, Xingdong; Zhao, Meng; Feng, Siliang; Zheng, Zhibing; Meng, Qingbin; Wang, Chenhong

doi:10.1002/psc.3306

Cited by 30 publications

(22 citation statements)

References 37 publications

(39 reference statements)

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“…Typically, such hybrid peptides entail reciprocal biophysical and biochemical interactions that depend on the amino acid sequence, its mobility and hydrophobicity. The amino acid sequence is believed to play a key role in achieving the correct structure and function of antimicrobial peptides [56]. However, amyloidogenic peptides can have a toxic effects on eukaryotic cells [57,58], which is an undesirable effect for the future use of AMPs in medicine [59].…”

Section: Introductionmentioning

confidence: 99%

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Grishin

Domnin

Кравченко

et al. 2021

IJMS

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The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as Pseudomonas aeruginosa, Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against P. aeruginosa.

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Section: Introductionmentioning

confidence: 99%

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Grishin

Domnin

Кравченко

et al. 2021

IJMS

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“…Moreover, the net‐positive charge was increased in the analogs peptides, which is a known factor that assists electrostatic interactions between AMPs and bacterial surfaces (negatively charged) (Fensterseifer et al, 2019). Finally, it is important to highlight that by preserving the hydrophobic moment and decreasing the overall peptides, hydrophobicity we generate potential AMPs that are potentially not toxic to mammalian healthy cells (hydrophobicity higher than 50% is commonly reported for hemolytic and cytotoxic AMPs) (Takahashi et al, 2010; Wang et al, 2021). Furthermore, the total of 22 AMP deposited in Antimicrobial Peptides Database with 13 amino acid residues and more than 50% amphipathicity were hemolytic (Wang et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Synthetic peptides bioinspired in temporin‐PTa with antibacterial and antibiofilm activity

et al. 2022

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Several antimicrobial peptides (AMPs) have been reported in amphibian toxins, as temporin‐PTa from Hylarana picturata. The amino acid distribution within a helical structure of AMPs favors the design of new bioactive peptides. Therefore, this work reports the rational design of two new synthetic peptides denominated Hp‐MAP1 and Hp‐MAP2 derived from temporin‐PTa. These peptides present an amphipathic helix with positive charges of +4 and +5, hydrophobic moment (<µH>) of 0.66 and 0.72 and hydrophobicity () of 0.49 and 0.41, respectively. Hp‐MAP1 and Hp‐MAP2 displayed in vitro activity against Gram‐negative and Gram‐positive bacteria from 2.8 to 92 µM, without presenting hemolytic effects. Molecular dynamics simulation suggested that the parent and designed temporin‐like peptides lack structural stability in an aqueous solution. By contrast, α‐helical structures were predicted in hydrophobic and anionic environments. Additionally, the peptides were simulated on mimetic membranes composed of anionic and neutral phospholipids 1,2‐dipalmitoylsn‐glycerol‐3‐phosphatidylglycerol (DPPG‐anionic), 1,2‐dipalmitoyl‐sn‐lyco‐3 phosphatidylethanolamine (DPPE‐neutral). When in contact with DPPG/DPPE (90:10) and DPPG/DPPE (50:50) temporin‐PTa, Hp‐MAP1 and Hp‐MAP2 established interactions guided by hydrogen and saline bounds. Therefore, the findings described here reveal that the optimization of the amphipathic α‐helical cationic peptides Hp‐MAP1 and Hp‐MAP2 enabled the generation of new synthetic antimicrobial agents to combat pathogenic microorganisms.

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“…The rate of hemolysis and cytotoxicity is a crucial factor in the development of new synthetic peptides, being of great importance in the removal or reduction of this characteristic, when the objective is to develop new drugs, which can be achieved through modifications/substitutions of amino acids along the primary sequence, altering parameters of physicochemical characteristics such as net charge and hydrophobicity ( Takahashi et al, 2010 ; Wang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

First generation of multifunctional peptides derived from latarcin-3a from Lachesana tarabaevi spider toxin

et al. 2022

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The need for discovering new compounds that can act selectively on pathogens is becoming increasingly evident, given the number of deaths worldwide due to bacterial infections or tumor cells. New multifunctional biotechnological tools are being sought, including compounds present in spider venoms, which have high biotechnological potential. The present work aims to perform the rational design and functional evaluation of synthetic peptides derived from Lachesana tarabaevi spider toxin, known as latarcin-3a. The antimicrobial activity was tested against Gram-positive and -negative bacteria, with minimum inhibitory concentrations (MIC) between 4 and 128 μg.ml−1. Anti-biofilm tests were then performed to obtain MICs, where the peptides demonstrated activity from 4 to 128 μg.ml−1. In vitro cell cytotoxicity assays were carried out from tumor cell lines, lineages C1498, Kasumi-1, K-562, Jurkat, MOLT4, and Raji. Erythrocyte integrity was evaluated in the presence of synthetic peptides analog, which did not promote hemolysis at 128 μg.ml−1. The peptide that showed the best antibacterial activity was Lt-MAP3 and the best antitumor was Lt-MAP2. In conclusion, rational design of multifunctional antimicrobial peptides may be promising alternative tools in the treatment of emerging diseases such as bacterial infections and tumor cells.

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

Cited by 30 publications

References 37 publications

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

Synthetic peptides bioinspired in temporin‐PTa with antibacterial and antibiofilm activity

First generation of multifunctional peptides derived from latarcin-3a from Lachesana tarabaevi spider toxin

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