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引用次数: 0
摘要
DNA 编码文库(DEL)技术是药物研究的重要工具,它能从大量化合物中快速鉴定出与感兴趣的靶点结合的化合物。在这项研究中,我们提出了一种在 3' 端生成含有化合物的单链 DEL(ssDEL)的新方法。通过引入独特设计的含脱氧尿苷(NC-HP)的发夹状头饰和使用一种裂解酶,可将双链 DELs(dsDELs)转化为这种 ssDELs。此外,Klenow 填料还为dsDELs 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能表现出耐久性,并能以高信噪比进行光交联,这在基于细胞的光交联选择中也得到了证实。
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' 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.
期刊介绍:
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