ArticleMolecular pharmaceutics2014
Antibacterial activities of amphiphilic cyclic cell-penetrating peptides against multidrug-resistant pathogens.
Article in Molecular pharmaceutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Targeted Design of Novel Antimicrobial Peptides againstACS omega · 2026Article
- Antimicrobial peptides in anti-infective and immunomodulatory applications: Mechanisms, challenges, and emerging computational design.Zoological research · 2026Review
- Alternative approaches in combating antimicrobial resistance in animals.Archives of microbiology · 2026Review
- Novel cyclic heptapeptides as potential therapeutics against methicillin-resistant Staphylococcus aureus infections.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Cyclic-Linear Hybrid Peptides as Molecular Transporters of Chemotherapeutic Agents.Chemical biology letters · 2026Article
- Anti-SARS-CoV-2 VHH and C7C peptide fused with Angiopep-2 efficiently traverse blood-brain barrier model and neutralizes virus.Frontiers in microbiology · 2026Article
- Design of Hybrid Bioactive Peptides Derived From Cecropin and Cathepsin for Therapeutic Application.Chemical biology & drug design · 2025Article
- Additive Effects ofInternational journal of molecular sciences · 2025Article
- Strong Membrane Permeabilization Activity Can Reduce Selectivity of Cyclic Antimicrobial Peptides.The journal of physical chemistry. B · 2025Article
- Antibacterial and Antifungal Activities of Linear and Cyclic Peptides Containing Arginine, Tryptophan, and Diphenylalanine.Antibiotics (Basel, Switzerland) · 2025Article
- The effects of cyclic peptide [R4W4] in combination with first-line therapy on the survival ofFrontiers in cellular and infection microbiology · 2025Article
- Nanoparticles with Cell-Penetrating Peptides for Oral Delivery: A Case for Oral Delivery of Insulin.International journal of nanomedicine · 2025Review
- Mechanistic Study of Antimicrobial Effectiveness of Cyclic Amphipathic Peptide [RAntibiotics (Basel, Switzerland) · 2024Article
- Antimicrobial and Adjuvant Potencies of Di-Antibiotics (Basel, Switzerland) · 2023Article
- Additive Effects of Cyclic Peptide [R4W4] When Added Alongside Azithromycin and Rifampicin againstPathogens (Basel, Switzerland) · 2023Article
- Structure-activity relationships of antibacterial peptides.Microbial biotechnology · 2023Review
- Functional insights to the development of bioactive material for combating bacterial infections.Frontiers in bioengineering and biotechnology · 2023Review
- Membrane-Active Cyclic Amphiphilic Peptides: Broad-Spectrum Antibacterial Activity Alone and in Combination with Antibiotics.Journal of medicinal chemistry · 2022Article
- Delineating the Mechanism of Action of a Protease Resistant and Salt Tolerant Synthetic Antimicrobial Peptide againstACS omega · 2022Article
- Head-to-tail cyclization of side chain-protected linear peptides to recapitulate genetically-encoded cyclized peptides.Peptide science (Hoboken, N.J.) · 2022Article
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Authors and funding
6 authors.
Funding
Abstract
Multidrug-resistant pathogens have become a major public health concern. There is a great need for the development of novel antibiotics with alternative mechanisms of action for the treatment of life-threatening bacterial infections. Antimicrobial peptides, a major class of antibacterial agents, share amphiphilicity and cationic structural properties with cell-penetrating peptides (CPPs). Herein, several amphiphilic cyclic CPPs and their analogues were synthesized and exhibited potent antibacterial activities against multidrug-resistant pathogens. Among all the peptides, cyclic peptide [R4W4] (1) showed the most potent antibacterial activity against methicillin-resistant Staphylococcus aureus [MRSA, exhibiting a minimal inhibitory concentration (MIC) of 2.67 μg/mL]. Cyclic [R4W4] and the linear counterpart R4W4 exhibited MIC values of 42.8 and 21.7 μg/mL, respectively, against Pseudomonas aeruginosa. In eukaryotic cells, peptide 1 exhibited the expected cell penetrating properties and showed >84% cell viability at a concentration of 15 μM (20.5 μg/mL) in three different human cell lines. Twenty-four hour time-kill studies evaluating [R4W4] with 2 times the MIC in combination with tetracycline demonstrated bactericidal activity at 4 and 8 times the MIC of tetracycline against MRSA (MIC = 0.5 μg/mL) and 2-8 times the MIC against Escherichia coli (MIC = 2 μg/mL). This study suggests that when amphiphilic cyclic CPPs are used in combination with an antibiotic such as tetracycline, they provide significant benefit against multidrug-resistant pathogens when compared with the antibiotic alone.
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