连接器
组合化学
烷基
DNA
寡核苷酸
化学
酰胺
化学合成
分子
药物发现
DNA合成
立体化学
生物化学
计算机科学
有机化学
体外
操作系统
作者
Zhaomei Sun,Shao‐Guang Yang,Xue Li,Jie Zhang,Kexin Yang,Yun Jin Hu
标识
DOI:10.1002/asia.202200016
摘要
A series of novel N-alkyl linkers that connect small-molecule library members with their encoding DNA oligonucleotides has been developed. In comparison with the standard amide linker (usually constructed with oligo-AOP-NH2 ), the N-alkyl linker is not only more chemically stable, but also provides better structural diversity at the linkage point. Chemical variety in the vicinity of the polyglycol terminus, in particular, could affect binding interactions with the target protein. It could have been neglected in previous DNA-encoded chemical library (DEL) synthesis and screening studies due to the limited linkage alternatives. With these linkers, one can produce versatile key intermediates as Cycle 1 products directly amenable to Cycle 2 chemistry without the use of protecting groups. As a result, a DEL synthesis process that uses the fewest chemical conversions, such as 3-step, 3-cycle DELs, can achieve higher synthetic efficiency while creating less DNA tag degradation, resulting in higher quality DELs.
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