ArticlePharmaceuticals (Basel, Switzerland)2014
"Specificity Determinants" Improve Therapeutic Indices of Two Antimicrobial Peptides Piscidin 1 and Dermaseptin S4 Against the Gram-negative Pathogens Acinetobacter baumannii and Pseudomonas aeruginosa.
Article in Pharmaceuticals (Basel, Switzerland), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Antibacterial activity of peptide derivatives of dermaseptins against multidrug-resistantBiochemistry and biophysics reports · 2026Article
- Smart Antibiofilm Platforms Based on Synthetic Antimicrobial Peptides-Engineered Hydrogels.Polymers · 2026Review
- Investigating How Lysophosphatidylcholine and Lysophosphatidylethanolamine Enhance the Membrane Permeabilization Efficacy of Host Defense Peptide Piscidin 1.The journal of physical chemistry. B · 2025Article
- Evaluation of the Antibacterial Activity of New Dermaseptin Derivatives againstPharmaceuticals (Basel, Switzerland) · 2024Article
- Host-defense piscidin peptides as antibiotic adjuvants against Clostridioides difficile.PloS one · 2024Article
- GATR-3, a Peptide That Eradicates Preformed Biofilms of Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2023Article
- Going Beyond Host Defence Peptides: Horizons of Chemically Engineered Peptides for Multidrug-Resistant Bacteria.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Thurincin H Is a Nonhemolytic Bacteriocin of Bacillus thuringiensis with Potential for Applied Use.Probiotics and antimicrobial proteins · 2023Article
- Recent Advances in Antimicrobial Peptide Hydrogels.International journal of molecular sciences · 2023Review
- Rational design of stapled antimicrobial peptides.Amino acids · 2023Review
- Designed Multifunctional Peptides for Intracellular Targets.Antibiotics (Basel, Switzerland) · 2022Review
- Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria.International journal of molecular sciences · 2022Article
- dbAMP 2.0: updated resource for antimicrobial peptides with an enhanced scanning method for genomic and proteomic data.Nucleic acids research · 2022Article
- Raja 42, a novel gamma lactam compound, is effective against Clostridioides difficile.PloS one · 2021Article
- Article
- ABC Exporters in Pathogenesis: Role of Synthetic Anti-Microbial Peptides.The protein journal · 2020Article
- The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells.Molecules (Basel, Switzerland) · 2020Article
- Positively Charged Polymers as Promising Devices against Multidrug Resistant Gram-Negative Bacteria: A Review.Polymers · 2020Review
- Structure and Function of an Inflammatory Cytokine, Interleukin-2, Analyzed Using the Bioinformatic Approach.The protein journal · 2019Article
- Redesigning Arenicin-1, an Antimicrobial Peptide from the Marine PolychaetaMarine drugs · 2019Article
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Authors and funding
4 authors.
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Abstract
A new class of antimicrobial agents with lower rates of resistance and different targets is urgently needed because of the rapidly increasing resistance to classical antibiotics. Amphipathic cationic α-helical antimicrobial peptides (AMPs) represent such a class of compounds. In our previous studies, using a 26-residue de novo designed antimicrobial peptide, we proposed the concept of "specificity determinant(s)": positively charged residue(s) in the center of the non-polar face of AMPs that could decrease hemolytic activity/toxicity but increase or maintain the same level of antimicrobial activity to increase dramatically the therapeutic index. In the current study, we used d-enantiomers of two AMPs, Piscidin 1 isolated from fish and dermaseptin S4 isolated from frog. We substituted different positions in the center of the hydrophobic face with one or two lysine residue(s) (one or two "specificity determinant(s)"). This simple modification not only maintained or improved antimicrobial activity against Gram-negative pathogens Acinetobacter baumannii (11 strains) and Pseudomonas aeruginosa (6 strains), but also dramatically decreased hemolytic activity of human red blood cells, as predicted. Therapeutic indices improved by 55-fold and 730-fold for piscidin 1 (I9K) and dermaseptin S4 (L7K, A14K), respectively, against A. baumannii. Similarly, the therapeutic indices improved 32-fold and 980-fold for piscidin 1 (I9K) and dermaseptin S4 (L7K, A14K), respectively, against P. aeruginosa.
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