ArticleACS chemical biology2013
Synthetic molecular evolution of pore-forming peptides by iterative combinatorial library screening.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Strong Membrane Permeabilization Activity Can Reduce Selectivity of Cyclic Antimicrobial Peptides.The journal of physical chemistry. B · 2025Article
- pH-Responsive Peptide Nanoparticles Deliver Macromolecules to Cells via Endosomal Membrane Nanoporation.ACS nano · 2024Article
- Cytosolic Delivery of Bioactive Cyclic Peptide Cargo by Spontaneous Membrane Translocating Peptides.ACS omega · 2024Article
- Design of Membrane Active Peptides Considering Multi-Objective Optimization for Biomedical Application.Membranes · 2022Review
- Synthetic Molecular Evolution of Cell Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Applications and evolution of melittin, the quintessential membrane active peptide.Biochemical pharmacology · 2021Review
- pH-triggered pore-forming peptides with strong composition-dependent membrane selectivity.Biophysical journal · 2021Article
- Broad-Spectrum Antiviral Entry Inhibition by Interfacially Active Peptides.Journal of virology · 2020Article
- Synthetic molecular evolution of host cell-compatible, antimicrobial peptides effective against drug-resistant, biofilm-forming bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mechanistic Landscape of Membrane-Permeabilizing Peptides.Chemical reviews · 2019Review
- Application of Synthetic Molecular Evolution to the Discovery of Antimicrobial Peptides.Advances in experimental medicine and biology · 2019Review
- DNA scaffolds support stable and uniform peptide nanopores.Nature nanotechnology · 2018Article
- Synthetic molecular evolution of hybrid cell penetrating peptides.Nature communications · 2018Article
- Outer membrane protein design.Current opinion in structural biology · 2017Review
- pH-Triggered, Macromolecule-Sized Poration of Lipid Bilayers by Synthetically Evolved Peptides.Journal of the American Chemical Society · 2017Article
- Host Cell Interactions Are a Significant Barrier to the Clinical Utility of Peptide Antibiotics.ACS chemical biology · 2016Article
- Conformational Fine-Tuning of Pore-Forming Peptide Potency and Selectivity.Journal of the American Chemical Society · 2015Article
- Mechanism Matters: A Taxonomy of Cell Penetrating Peptides.Trends in biochemical sciences · 2015Review
- Highly efficient macromolecule-sized poration of lipid bilayers by a synthetically evolved peptide.Journal of the American Chemical Society · 2014Article
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5 authors.
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Abstract
We previously reported the de novo design of a combinatorial peptide library that was subjected to high-throughput screening to identify membrane-permeabilizing antimicrobial peptides that have β-sheet-like secondary structure. Those peptides do not form discrete pores in membranes but instead partition into membrane interfaces and cause transient permeabilization by membrane disruption, but only when present at high concentration. In this work, we used a consensus sequence from that initial screen as a template to design an iterative, second generation library. In the 24-26-residue, 16,200-member second generation library we varied six residues. Two diad repeat motifs of alternating polar and nonpolar amino acids were preserved to maintain a propensity for non-helical secondary structure. We used a new high-throughput assay to identify members that self-assemble into equilibrium pores in synthetic lipid bilayers. This screen was done at a very stringent peptide to lipid ratio of 1:1000 where most known membrane-permeabilizing peptides, including the template peptide, are not active. In a screen of 10,000 library members we identified 16 (~0.2%) that are equilibrium pore-formers at this high stringency. These rare and highly active peptides, which share a common sequence motif, are as potent as the most active pore-forming peptides known. Furthermore, they are not α-helical, which makes them unusual, as most of the highly potent pore-forming peptides are amphipathic α-helices. Here we demonstrate that this synthetic molecular evolution-based approach, taken together with the new high-throughput tools we have developed, enables the identification, refinement, and optimization of unique membrane active peptides.
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