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A Single‐Stranded DNA‐Encoded Chemical Library Based on a Stereoisomeric Scaffold Enables Ligand Discovery by Modular Assembly of Building Blocks
Advanced Science ( IF 15.1 ) Pub Date : 2020-10-14 , DOI: 10.1002/advs.202001970
Gabriele Bassi 1 , Nicholas Favalli 1 , Miriam Vuk 1 , Marco Catalano 1 , Adriano Martinelli 1 , Anika Trenner 2 , Antonio Porro 2 , Su Yang 3 , Chuin Lean Tham 4 , Mustafa Moroglu 5 , Wyatt W Yue 4 , Stuart J Conway 5 , Peter K Vogt 3 , Alessandro A Sartori 2 , Jörg Scheuermann 1 , Dario Neri 1
Affiliation  

A versatile and Lipinski‐compliant DNA‐encoded library (DEL), comprising 366 600 glutamic acid derivatives coupled to oligonucleotides serving as amplifiable identification barcodes is designed, constructed, and characterized. The GB‐DEL library, constructed in single‐stranded DNA format, allows de novo identification of specific binders against several pharmaceutically relevant proteins. Moreover, hybridization of the single‐stranded DEL with a set of known protein ligands of low to medium affinity coupled to a complementary DNA strand results in self‐assembled selectable chemical structures, leading to the identification of affinity‐matured compounds.

中文翻译:

基于立体异构支架的单链 DNA 编码化学文库可通过构建模块的模块化组装来发现配体

设计、构建并表征了一个多功能且符合 Lipinski 标准的 DNA 编码库 (DEL),其中包含与寡核苷酸偶联的 366 600 个谷氨酸衍生物,用作可扩增的识别条形码。GB-DEL 文库以单链 DNA 格式构建,可以从头鉴定针对几种药学相关蛋白的特异性结合剂。此外,单链 DEL 与一组已知的低至中等亲和力的蛋白质配体杂交,并与互补的 DNA 链偶联,产生自组装的选择性化学结构,从而鉴定出亲和力成熟的化合物。
更新日期:2020-11-19
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