Niwa Masatoshi, Hayashida Jun, Tokugawa Munefumi, Nanya Takeshi, Tanabe Masako, Honda Naoko, Inohana Takehiko, Fukano Hajime, Shigeta Yukihiro, Kuboyama Takeshi, Itoh Shin
Chemical Research Laboratories, Nissan Chemical Corporation, 10-1 Tsuboi-Nishi 2-chome, Funabashi, Chiba, Japan.
Biological Research Laboratories, Nissan Chemical Corporation, 1470, Shiraoka, Shiraoka, Saitama, Japan.
Chemistry. 2024 Dec 23;30(72):e202403233. doi: 10.1002/chem.202403233. Epub 2024 Nov 19.
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.
DNA编码文库（DEL）技术是药物研究中的关键工具，可从大量化合物中快速识别与目标靶点结合的化合物。在本研究中，我们提出了一种在3'端带有化合物生成单链DEL（ssDEL）的新方法。引入含有脱氧尿苷的独特设计的发夹形头部（NC-HP）以及使用切割酶有助于双链DEL（dsDEL）转化为此类ssDEL。此外，Klenow补平为dsDEL提供了与编码区共价连接的光交联剂，即使在严格的洗涤条件下也具有耐久性，并能实现高信噪比的光交联，这在基于细胞的光交联筛选中也得到了证实。
