Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery
Protein-Observed Fluorine NMR: A Bioorthogonal Approach for Small Molecule Discovery
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DOI：
10.1021/acs.jmedchem.5b01447
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发表时间：
2016-06-09
影响因子：
7.3
通讯作者：
Pomerantz, William C. K.
中科院分区：
文献类型：
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作者：
Arntson, Keith E.;Pomerantz, William C. K.
F-19同位素是100%天然丰富的，是第二个最敏感和最稳定的NMR活性核。与无处不在的氢原子不同，氟在生物系统中几乎不存在，使其成为探测生物学中分子相互作用的独特生物正交原子。自1974年船体和赛克斯开创性的研究以来，已经用F-19 NMR研究了73种以上的氟化蛋白质。随着冷冻探针生产和氟化氨基酸掺入策略的进步，基于蛋白质的F-19 NMR为药物化学家提供了表征并最终发现新的小分子蛋白质配体的机会。这篇综述将突出使用F-19 NMR表征小分子与小蛋白和大蛋白相互作用的新进展，并详细介绍NMR共振分配挑战和氨基酸掺入方法。
The F-19 isotope is 100% naturally abundant and is the second most sensitive and stable NMR-active nucleus. Unlike the ubiquitous hydrogen atom, fluorine is nearly absent in biological systems, making it a unique bioorthogonal atom for probing molecular interactions in biology. Over 73 fluorinated proteins have been studied by F-19 NMR since the seminal studies of Hull and Sykes in 1974. With advances in cryoprobe production and fluorinated amino acid incorporation strategies, protein-based F-19 NMR offers opportunities to the medicinal chemist for characterizing and ultimately discovering new small molecule protein ligands. This review will highlight new advances using F-19 NMR for characterizing small molecule interactions with both small and large proteins as well as detailing NMR resonance assignment challenges and amino acid incorporation approaches.