Dalvit Claudio, Knapp Stefan
Faculty of Science, University of Neuchatel, 2000, Neuchatel, Switzerland.
Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Riedberg Campus, 60438, Frankfurt, Germany.
Magn Reson Chem. 2017 Dec;55(12):1091-1095. doi: 10.1002/mrc.4640. Epub 2017 Aug 24.
Fluorine ligand-based NMR spectroscopy is now an established method for performing binding screening against a macromolecular target. Typically, the transverse relaxation rate of the fluorine signals is monitored in the absence and presence of the target. However, useful structural information can sometimes be obtained from the analysis of the fluorine isotropic chemical shift. This is particularly relevant for molecules that are racemates and/or display multiple conformers. The large difference in fluorine isotropic chemical shift between free and bound state deriving mainly from the breaking and/or making of intramolecular and/or intermolecular hydrogen bonds allows the detection of very weak affinity ligands. According to our experimental results, racemates should always be included in the generation of the fluorinated fragment libraries. The selection or the availability of only one of the enantiomers for the fluorinated screening library could result in missing relevant chemical scaffold motifs.
基于氟配体的核磁共振光谱法现已成为针对大分子靶标进行结合筛选的既定方法。通常，在不存在和存在靶标的情况下监测氟信号的横向弛豫率。然而，有时可以从氟各向同性化学位移的分析中获得有用的结构信息。这对于外消旋体和/或显示多种构象的分子尤为重要。游离态和结合态之间氟各向同性化学位移的巨大差异主要源于分子内和/或分子间氢键的断裂和/或形成，这使得能够检测到亲和力非常弱的配体。根据我们的实验结果，在外消旋体生成氟化片段库时应始终将其包括在内。氟化筛选库中仅选择一种对映体或仅可获得一种对映体可能会导致遗漏相关的化学支架基序。
