Impact of a Central Scaffold on the Binding Affinity of Fragment Pairs Isolated from DNA-Encoded Self-Assembling Chemical Libraries
Impact of a Central Scaffold on the Binding Affinity of Fragment Pairs Isolated from DNA-Encoded Self-Assembling Chemical Libraries
复制标题
DOI：
10.1002/cmdc.201700569
复制
发表时间：
2017-11-08
期刊：
影响因子：
3.4
通讯作者：
Sladojevich, Filippo
中科院分区：
文献类型：
--
作者：
Bigatti, Martina;Dal Corso, Alberto;Sladojevich, Filippo
编码的自组装化学文库的筛选允许鉴定与感兴趣的靶蛋白上的相邻口袋结合的片段对。对于实际应用，有必要将这些配体对连接成不含任何核酸组分的离散有机分子。在这里，我们描述了一个协同结合对酸性α-1糖蛋白的发现和化学策略，用于识别最佳接头，连接两个片段。该程序产生了一组小的有机配体，其中最好的表现出9.9 nm的解离常数，在溶液中通过荧光偏振测量。
The screening of encoded self-assembling chemical libraries allows the identification of fragment pairs that bind to adjacent pockets on target proteins of interest. For practical applications, it is necessary to link these ligand pairs into discrete organic molecules, devoid of any nucleic acid component. Here we describe the discovery of a synergistic binding pair for acid alpha-1 glycoprotein and a chemical strategy for the identification of optimal linkers, connecting the two fragments. The procedure yielded a set of small organic ligands, the best of which exhibited a dissociation constant of 9.9 nm, as measured in solution by fluorescence polarization.