ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
A miniature mimic of host defense peptides with systemic antibacterial efficacy.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- An efflux-susceptible antibiotic-adjuvant with systemic efficacy against mouse infections.Scientific reports · 2022Article
- Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics.ACS infectious diseases · 2022Review
- LEGO-Lipophosphonoxins: A Novel Approach in Designing Membrane Targeting Antimicrobials.Journal of medicinal chemistry · 2022Article
- Review
- Mechanistic Studies of Antibiotic Adjuvants Reducing Kidney's Bacterial Loads upon Systemic Monotherapy.Pharmaceutics · 2021Article
- A broad-spectrum bactericidal lipopeptide with anti-biofilm properties.Scientific reports · 2017Article
- Cationic Net Charge and Counter Ion Type as Antimicrobial Activity Determinant Factors of Short Lipopeptides.Frontiers in microbiology · 2017Article
- Sensitization of Gram-negative bacteria to rifampin and OAK combinations.Scientific reports · 2015Article
- Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes.Biochimica et biophysica acta · 2014Article
- Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs.Pharmaceuticals (Basel, Switzerland) · 2013Article
- New horizons for host defense peptides and lantibiotics.Current opinion in pharmacology · 2012Review
- Antibacterial properties of an oligo-acyl-lysyl hexamer targeting Gram-negative species.Antimicrobial agents and chemotherapy · 2012Article
- Efficacy of OH-CATH30 and its analogs against drug-resistant bacteria in vitro and in mouse models.Antimicrobial agents and chemotherapy · 2012Article
- Decoding the functional roles of cationic side chains of the major antimicrobial region of human cathelicidin LL-37.Antimicrobial agents and chemotherapy · 2012Article
- The oligo-acyl lysyl antimicrobial peptide C₁₂K-2β₁₂ exhibits a dual mechanism of action and demonstrates strong in vivo efficacy against Helicobacter pylori.Antimicrobial agents and chemotherapy · 2012Article
- Antiplasmodial properties of acyl-lysyl oligomers in culture and animal models of malaria.Antimicrobial agents and chemotherapy · 2011Article
- Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches.Cellular and molecular life sciences : CMLS · 2011Review
- Mechanisms mediating bactericidal properties and conditions that enhance the potency of a broad-spectrum oligo-acyl-lysyl.Antimicrobial agents and chemotherapy · 2011Article
- Experimental conditions that enhance potency of an antibacterial oligo-acyl-lysyl.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Oligomers of acylated lysines (OAKs) are synthetic mimics of host defense peptides (HDPs) with promising antimicrobial properties. Here we challenged the OAK concept for its ability to generate both systemically efficient and economically viable lead compounds for fighting multidrug-resistant bacteria. We describe the design and characterization of a miniature OAK composed of only 3 lysyls and 2 acyls (designated C(12(omega7))K-beta(12)) that preferentially targets gram-positive species by a bacteriostatic mode of action. To gain insight into the mechanism of action, we examined the interaction of OAK with various potential targets, including phospholipid bilayers, using surface plasmon resonance, and Langmuir monolayers, using insertion assays, epifluorescence microscopy, and grazing incidence X-ray diffraction, in a complementary manner. Collectively, the data support the notion that C(12(omega7))K-beta(12) damages the plasma-membrane architecture similarly to HDPs, that is, following a near-classic 2-step interaction including high-affinity electrostatic adhesion and a subsequent shallow insertion that was limited to the phospholipid head group region. Notably, preliminary acute toxicity and efficacy studies performed with mouse models of infection have consolidated the potential of OAK for treating bacterial infections, including systemic treatments of methicillin-resistant Staphylococcus aureus. Such simple yet robust chemicals might be useful for various antibacterial applications while circumventing potential adverse effects associated with cytolytic compounds.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.