ArticleNature chemistry2022
A mating mechanism to generate diversity for the Darwinian selection of DNA-encoded synthetic molecules.
Article in Nature chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- One-pot multi-substrate screening of ligation reactions using PNA tags.Chemical science · 2026Article
- A tailored CoA ligase-Nature catalysis · 2026Article
- Discovery of d‑Miniprotein Inhibitors of PD-1/PD-L1 Interaction via Mirror-Image Phage Display against Synthetic d‑PD‑1.JACS Au · 2025Article
- Activation of PD-1/PD-L1 immune checkpoint by Zika virus.PLoS pathogens · 2025Article
- Evolution of multivalent supramolecular assemblies of aptamers with target-defined spatial organization.Nature nanotechnology · 2025Article
- A method to identify small molecule/protein pairs susceptible to protein ubiquitination by the CRBN E3 ligase.Chemical science · 2025Article
- Flexibility-tuning of dual-display DNA-encoded chemical libraries facilitates cyclic peptide ligand discovery.Nature communications · 2025Article
- Development of supramolecular anticoagulants with on-demand reversibility.Nature biotechnology · 2025Article
- Translation of Deoxyribonucleic Acid into Synthetic Alpha Helical Peptides for Darwinian Evolution.JACS Au · 2024Article
- Protein-templated ligand discovery via the selection of DNA-encoded dynamic libraries.Nature chemistry · 2024Article
- Recording Binding Information Directly into DNA-Encoded Libraries Using Terminal Deoxynucleotidyl Transferase.Journal of the American Chemical Society · 2023Article
- Trio-pharmacophore DNA-encoded chemical library for simultaneous selection of fragments and linkers.Nature communications · 2023Article
- Photochemical Methods Applied to DNA Encoded Library (DEL) Synthesis.Accounts of chemical research · 2023Article
- Towards the controlled enzymatic synthesis of LNA containing oligonucleotides.Frontiers in chemistry · 2023Article
- Aryl diazonium intermediates enable mild DNA-compatible C-C bond formation for medicinally relevant combinatorial library synthesis.Chemical science · 2022Article
- Recent advances in DNA-encoded dynamic libraries.RSC chemical biology · 2022Review
- Converting Double-Stranded DNA-Encoded Libraries (DELs) to Single-Stranded Libraries for More Versatile Selections.ACS omega · 2022Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA-encoded library technologies enable the screening of synthetic molecules but have thus far not tapped into the power of Darwinian selection with iterative cycles of selection, amplification and diversification. Here we report a simple strategy to rapidly assemble libraries of conformationally constrained peptides that are paired in a combinatorial fashion (suprabodies). We demonstrate that the pairing can be shuffled after each amplification cycle in a process similar to DNA shuffling or mating to regenerate diversity. Using simulations, we show the benefits of this recombination in yielding a more accurate correlation of selection fitness with affinity after multiple rounds of selection, particularly if the starting library is heterogeneous in the concentration of its members. The method was validated with selections against streptavidin and applied to the discovery of PD-L1 binders. We further demonstrate that the binding of self-assembled suprabodies can be recapitulated by smaller (∼7 kDa) synthetic products that maintain the conformational constraint of the peptides.
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