Enzymatic Cleavage of Double-Stranded DNA-Encoded Libraries (DELs) to Single-Stranded DELs with Compounds at the 3' End: Its Application in Photo-Crosslinking Selection

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' en...

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Bibliographic Details
Published in:Chemistry : a European journal 2024-11, p.e202403233
Main Authors: Niwa, Masatoshi, Hayashida, Jun, Tokugawa, Munefumi, Nanya, Takeshi, Tanabe, Masako, Honda, Naoko, Inohana, Takehiko, Fukano, Hajime, Shigeta, Yukihiro, Kuboyama, Takeshi, Itoh, Shin
Format: Article
Language:English
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Summary: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. Moreover, Klenow fill-in provides the dsDELs with photo-crosslinkers covalently linked to the coding region, which exhibit durability even under stringent washing conditions and enable photo-crosslinking with a high signal-to-noise ratio, as also confirmed in cell-based photo-crosslinking selections.
ISSN:0947-6539
1521-3765
1521-3765
DOI:10.1002/chem.202403233