Becker Bridget A, Larive Cynthia K
Department of Chemistry, University of California, Riverside, Riverside, California 92521, USA.
J Phys Chem B. 2008 Oct 30;112(43):13581-7. doi: 10.1021/jp8060366. Epub 2008 Oct 8.
Mapping the interactions of a small molecule ligand with a protein can provide information important for biochemical studies and for drug design and development. This information can be determined using the ligand-detected (1)H NMR experiments T(1rho)-NOESY, diffusion, and saturation transfer difference (STD). This work compares the results of these experiments and examines their ability to distinguish the binding epitopes of propranolol enantiomers with alpha 1-acid glycoprotein (AGP). The epitope maps for the propranolol enantiomers are fairly similar, as expected from their similar binding affinities; however, the STD epitope maps provide unique insights into the different orientations of the enantiomers with respect to the AGP binding pocket. Our results suggest that it is best to consider the data provided by several NMR epitope mapping experiments in drawing conclusions about ligand-protein binding interactions.
绘制小分子配体与蛋白质的相互作用图谱可为生物化学研究以及药物设计与开发提供重要信息。该信息可通过配体检测的（1）H NMR实验T（1ρ）-NOESY、扩散和饱和转移差异（STD）来确定。这项工作比较了这些实验的结果，并检验了它们区分普萘洛尔对映体与α1-酸性糖蛋白（AGP）结合表位的能力。正如预期的那样，由于普萘洛尔对映体具有相似的结合亲和力，其表位图相当相似；然而，STD表位图为对映体相对于AGP结合口袋的不同取向提供了独特的见解。我们的结果表明，在得出关于配体-蛋白质结合相互作用的结论时，最好考虑几个NMR表位图谱实验提供的数据。
