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,
{"title":"Van Leusen咪唑单粒单化合物dna编码文库的合成","authors":"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, ","doi":"10.1021/acs.bioconjchem.5c00317","DOIUrl":null,"url":null,"abstract":"<p >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.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"36 9","pages":"2013–2019"},"PeriodicalIF":3.9000,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Van Leusen Imidazole Synthesis for One-Bead-One-Compound DNA-Encoded Libraries\",\"authors\":\"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, \",\"doi\":\"10.1021/acs.bioconjchem.5c00317\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >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.</p>\",\"PeriodicalId\":29,\"journal\":{\"name\":\"Bioconjugate Chemistry\",\"volume\":\"36 9\",\"pages\":\"2013–2019\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioconjugate Chemistry\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.bioconjchem.5c00317\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioconjugate Chemistry","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.bioconjchem.5c00317","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Van Leusen Imidazole Synthesis for One-Bead-One-Compound DNA-Encoded Libraries
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
