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A versatile and Lipinski-compliant DNA-encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB-DEL library, constructed in single-stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single-stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self-assembled selectable chemical structures, leading to the identification of affinity-matured compounds.
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http://dx.doi.org/10.1002/advs.202001970 | DOI Listing |
Bioconjug Chem
July 2025
Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
The fluorescent dye-based simple and high-throughput DNA damage assay method was developed for the single-stranded DNA-encoded library (ssDEL) synthesis. The extent of DNA hybridization between single-stranded DNA (ssDNA) and its complementary DNA is influenced by the damage ratio of ssDNA. This damage can be quantified by measuring the change in the fluorescence of PicoGreen, providing valuable insights into the overall ssDNA integrity and facilitating the screening of DNA-compatible conditions for ssDEL synthesis.
View Article and Find Full Text PDFSci Adv
April 2025
South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou 510640, China.
DNA has demonstrated the abilities to differentiate single-wall carbon nanotubes (SWCNTs) with various chiralities and manipulate their analyte sensing properties. However, the fundamental mechanisms underlying these remarkable abilities remain unclear due to the lack of high-resolution determination of DNA structures on SWCNTs. Here, we combine atomic force microscopy and single-particle cryo-electron microscopy to determine DNA structures on five different types of single-chirality SWCNTs, achieving unprecedented subnanometer resolution.
View Article and Find Full Text PDFSLAS Discov
March 2025
WuXi AppTec, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China. Electronic address:
To date, RNA-targeted chemical matter is under explored due to a lack of robust screening assays. In this study, we present a novel RNA-targeted small molecule screening approach using a specialized DNA-encoded library (DEL). Our findings reveal that the specialized DEL library, called "DEL Zipper", can significantly reduce single-stranded DNA-RNA region interaction signals during various kinds of RNA selection.
View Article and Find Full Text PDFChemistry
December 2024
Chemical Research Laboratories, Nissan Chemical Corporation, 10-1 Tsuboi-Nishi 2-chome, Funabashi, Chiba, Japan.
DNA-encoded library (DEL) technology is a crucial tool in pharmaceutical research, rapidly identifying compounds that bind to a target of interest from an extensive pool of compounds. In this study, we propose a new method for generating single-stranded DELs (ssDELs) with compounds at the 3' end. The introduction of uniquely designed hairpin-shaped headpieces containing deoxyuridine (NC-HP) and the use of a cleavage enzyme facilitate the conversion from double-stranded DELs (dsDELs) to such ssDELs.
View Article and Find Full Text PDFFront Microbiol
July 2024
Faculty of Health Sciences, Universidad Científica del Sur, Lima, Peru.