ArticleScience advances2019
Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries.Chembiochem : a European journal of chemical biology · 2026Review
- Identification of Secondary Nucleation Inhibitors of Amyloid-β Aggregation by Cellular Selection of a SICLOPPS Library.Chembiochem : a European journal of chemical biology · 2026Article
- Phage-Assisted Continuous Selection of Bioactive Cyclic Peptides.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A genetically encoded selection for amyloid-β oligomer binders.Nature chemical biology · 2025Article
- Optimization of a High-Throughput Screen for Monitoring Disease-Associated Protein Misfolding and Aggregation in Bacteria.ACS synthetic biology · 2025Article
- Continuous selection in E. coli to identify cyclic peptide inhibitors of protein aggregation.Nature chemical biology · 2025Article
- Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection.Nature chemical biology · 2025Article
- Next Generation SICLOPPS Screening for the Identification of Inhibitors of the HIF-1α/HIF-1β Protein-Protein Interaction.ACS chemical biology · 2024Article
- Biotechnological and pharmaceutical potential of twenty-eight novel type strains ofCurrent research in microbial sciences · 2024Article
- The Discovery of Peptide Macrocycle Rescuers of Pathogenic Protein Misfolding and Aggregation by Integrating SICLOPPS Technology and Ultrahigh-Throughput Screening in Bacteria.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Pathological ATX3 Expression Induces Cell Perturbations inInternational journal of molecular sciences · 2021Article
- Recent Advances in the Application Peptide and Peptoid in Diagnosis Biomarkers of Alzheimer's Disease in Blood.Frontiers in molecular neuroscience · 2021Review
- Challenges and advances in genome mining of ribosomally synthesized and post-translationally modified peptides (RiPPs).Synthetic and systems biotechnology · 2020Review
- Editorial: Protein Aggregation and Solubility in Microorganisms (Archaea, Bacteria and Unicellular Eukaryotes): Implications and Applications.Frontiers in microbiology · 2020Article
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11 authors.
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Abstract
Protein misfolding and aggregation are associated with a many human disorders, including Alzheimer's and Parkinson's diseases. Toward increasing the effectiveness of early-stage drug discovery for these conditions, we report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities and their direct functional screening for discovering protein aggregation inhibitors. We illustrate this approach by performing, what is to our knowledge, the largest functional screen of small-size molecular entities described to date. We generated a combinatorial library of ~200 million drug-like, cyclic peptides and rapidly screened it for aggregation inhibitors against the amyloid-β peptide (Aβ42), linked to Alzheimer's disease. Through this procedure, we identified more than 400 macrocyclic compounds that efficiently reduce Aβ42 aggregation and toxicity in vitro and in vivo. Finally, we applied a combination of deep sequencing and mutagenesis analyses to demonstrate how this system can rapidly determine structure-activity relationships and define consensus motifs required for bioactivity.
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