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• W2947392804 endingPage "2026" @default.
• W2947392804 startingPage "2026" @default.
• W2947392804 abstract "Inspired by the many reported successful applications of DNA-encoded chemical libraries in drug discovery projects with protein targets, we decided to apply this platform to nucleic acid targets. We used a 120-billion-compound set of 33 distinct DNA-encoded chemical libraries and affinity-mediated selection to discover binders to a panel of DNA targets. Here, we report the successful discovery of small molecules that specifically interacted with DNA G-quartets, which are stable structural motifs found in G-rich regions of genomic DNA, including in the promoter regions of oncogenes. For this study, we chose the G-quartet sequence found in the c-myc promoter as a primary target. Compounds enriched using affinity-mediated selection against this target demonstrated high-affinity binding and high specificity over DNA sequences not containing G-quartet motifs. These compounds demonstrated a moderate ability to discriminate between different G-quartet motifs and also demonstrated activity in a cell-based assay, suggesting direct target engagement in the cell. DNA-encoded chemical libraries and affinity-mediated selection are uniquely suited to discover binders to targets that have no inherent activity outside of a cellular context, and they may also be of utility in other nucleic acid structural motifs." @default.
• W2947392804 created "2019-06-07" @default.
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• W2947392804 date "2019-05-27" @default.
• W2947392804 modified "2023-10-12" @default.
• W2947392804 title "Novel Nucleic Acid Binding Small Molecules Discovered Using DNA-Encoded Chemistry" @default.
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• W2947392804 doi "https://doi.org/10.3390/molecules24102026" @default.
• W2947392804 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6572338" @default.
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