Kim Hai-Young, Wyss Daniel F
Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ, 07033, USA,
Methods Mol Biol. 2015;1263:197-208. doi: 10.1007/978-1-4939-2269-7_16.
Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300-350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.
基于片段的药物设计（FBDD）包括用于寻找活性分子的基于片段的筛选（FBS）以及将这些活性分子优化为先导化合物。与高通量筛选得到的分子相比，典型的片段活性分子分子量较低（<300 - 350 Da），初始活性较低，但配体效率较高。核磁共振波谱法已广泛应用于基于片段的药物设计，因为它能识别和定位弱相互作用活性分子在靶蛋白上的结合位点。在此，我们描述了基于配体的核磁共振方法，用于从片段库中识别活性分子以及对主要活性分子进行功能交叉验证。
