ArticleNature communications2025
Flexibility-tuning of dual-display DNA-encoded chemical libraries facilitates cyclic peptide ligand discovery.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Unleashing the power of DNA-encoded libraries for challenging targets in drug discovery.Pharmaceutical science advances · 2026Review
- Synthesis of 2,3-(Diheterocyclyl)Propanoic Acid Esters as New Building Blocks via Complementary Meldrum's Acid and Aza-Michael Strategies.Molecules (Basel, Switzerland) · 2026Article
- Generation of membrane-permeable cyclic peptides inhibiting protein-protein interaction.Nature chemical biology · 2026Article
- Massive barcode-free chemical screenings enable the discovery of bioactive macrocycles with passive membrane permeability.Nature communications · 2026Article
- Linker Engineering in Stapled Peptides for Enhanced Membrane Permeability: Screening and Optimization Strategies.International journal of molecular sciences · 2026Review
- Late-stage peptide modification with salicylaldehyde tag enhances affinity for nuclear factor-kappa B essential modulator.RSC chemical biology · 2026Article
- A tailored CoA ligase-Nature catalysis · 2026Article
- Phenylalanine-Based DNA-Encoded Chemical Libraries for the Discovery of Potent and Selective Small Organic Ligands Against Markers of Cancer and Immune Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
11 authors.
Funding
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Abstract
Cyclic peptides constitute an important drug modality since they offer significant advantages over small molecules and macromolecules. However, access to diverse chemical sets of cyclic peptides is difficult on a large library scale. DNA-encoded Chemical Libraries (DELs) provide a suitable tool to obtain large chemical diversity, but cyclic DELs made by standard DEL implementation cannot efficiently explore their conformational diversity. On the other hand, dual-display Encoded Self-Assembling Chemical (ESAC) Libraries can be used for modulating macrocycle flexibility since the two displayed peptides can be connected in an incremental fashion. In this work, we construct a 56 million dual-display ESAC library using a two-step cyclization strategy. We show that varying the level of conformational restraint is essential for the discovery of specific ligands for the three protein targets thrombin, human alkaline phosphatase and streptavidin.
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