Yihui Xie, Mengtian Huang, Yanfen Jiang, Xiaoming Miao, Haopei Wang, Qi Zhang, Dongcheng Dai*, Xiangzhi Zeng, Qingmin Yang, Wenji Su, Alexander L. Satz* and Letian Kuai,
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引用次数: 0
Abstract
One-bead-one-compound (OBOC) DNA-encoded library (DEL) enables high-throughput activity-based screening to find novel hits against pharmaceutical targets. Herein, we developed solid-phase and DNA-compatible conditions to implement the three-component Van Leusen reaction (imidazole formation) for OBOC DELs. High-throughput validation was conducted (employing every potential building block) to simultaneously provide the groundwork for potential library synthesis and demonstrate the reagent scope. A total of 251 aldehydes, 380 amines, and 19 tosylmethyl isocyanides (TosMICs) were validated, with 65 aldehydes, 194 amines, and 15 TosMICs meeting the 50% yield cutoff. We take particular interest in aliphatic TosMICs because they yield more drug-like products. Encouragingly, aliphatic TosMICs perform well in solid-phase, but not solution-phase.
期刊介绍：
Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.
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