ArticleJournal of the American Chemical Society2015
Conformational Fine-Tuning of Pore-Forming Peptide Potency and Selectivity.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed.
- Mechanism-Driven Screening of Membrane-Targeting and Pore-Forming Antimicrobial Peptides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploration of bioactive variants of the BMP7-derived p[63-82] peptide for ameliorating the OA-associated chondrocyte phenotype.Arthritis research & therapy · 2025Article
- The difference between MelP5 and melittin membrane poration.Scientific reports · 2025Article
- QSAR Reveals Decreased Lipophilicity of Polar Residues Determines the Selectivity of Antimicrobial Peptide Activity.ACS omega · 2024Article
- Structural Determinants of Peptide Nanopore Formation.ACS nano · 2024Article
- Design of pH-responsive antimicrobial peptide melittin analog-camptothecin conjugates for tumor therapy.Asian journal of pharmaceutical sciences · 2024Article
- Dimerization and lysine substitution of melittin have differing effects on bacteria.Frontiers in pharmacology · 2024Article
- The reduced-charge melittin analogue MelP5 improves the transfection of non-viral DNA nanoparticles.Journal of peptide science : an official publication of the European Peptide Society · 2022Article
- Synthetic Molecular Evolution of Cell Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Predicting Membrane-Active Peptide Dynamics in Fluidic Lipid Membranes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Applications and evolution of melittin, the quintessential membrane active peptide.Biochemical pharmacology · 2021Review
- Membrane-selective nanoscale pores in liposomes by a synthetically evolved peptide: implications for triggered release.Nanoscale · 2021Article
- Chemical approaches in the development of natural nontoxic peptide Polybia-MP1 as a potential dual antimicrobial and antitumor agent.Amino acids · 2021Review
- Tuning of a Membrane-Perforating Antimicrobial Peptide to Selectively Target Membranes of Different Lipid Composition.The Journal of membrane biology · 2021Article
- Broad-Spectrum Antiviral Entry Inhibition by Interfacially Active Peptides.Journal of virology · 2020Article
- Article
- Antimicrobial Peptides: Classification, Design, Application and Research Progress in Multiple Fields.Frontiers in microbiology · 2020Review
- Honeybee venom and melittin suppress growth factor receptor activation in HER2-enriched and triple-negative breast cancer.NPJ precision oncology · 2020Article
- Article
- Mechanistic Landscape of Membrane-Permeabilizing Peptides.Chemical reviews · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
To better understand the sequence-structure-function relationships that control the activity and selectivity of membrane-permeabilizing peptides, we screened a peptide library, based on the archetypal pore-former melittin, for loss-of-function variants. This was accomplished by assaying library members for failure to cause leakage of entrapped contents from synthetic lipid vesicles at a peptide-to-lipid ratio of 1:20, 10-fold higher than the concentration at which melittin efficiently permeabilizes the same vesicles. Surprisingly, about one-third of the library members are inactive under these conditions. In the negative peptides, two changes of hydrophobic residues to glycine were especially abundant. We show that loss-of-function activity can be completely recapitulated by a single-residue change of the leucine at position 16 to glycine. Unlike the potently cytolytic melittin, the loss-of-function peptides, including the single-site variant, are essentially inactive against phosphatidylcholine vesicles and multiple types of eukaryotic cells. Loss of function is shown to result from a shift in the binding-folding equilibrium away from the active, bound, α-helical state toward the inactive, unbound, random-coil state. Accordingly, the addition of anionic lipids to synthetic lipid vesicles restored binding, α-helical secondary structure, and potent activity of the "negative" peptides. While nontoxic to mammalian cells, the single-site variant has potent bactericidal activity, consistent with the anionic nature of bacterial membranes. The results show that conformational fine-tuning of helical pore-forming peptides is a powerful way to modulate their activity and selectivity.
Indexed as
Identifiers
What OpenQuestion holds
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.