Chung Florence, Tisné Carine, Lecourt Thomas, Seijo Bili, Dardel Frédéric, Micouin Laurent
Chimie Thérapeutique, Université Paris Descartes, CNRS, UMR 8638, 4 avenue de l'Observatoire, 75006 Paris, France.
Chemistry. 2009 Jul 20;15(29):7109-16. doi: 10.1002/chem.200802451.
A fragment-based approach for the synthesis of ligands of tRNA(Lys) (3), the HIV reverse-transcription primer, is described. The use of NMR spectroscopy has proved to be very useful in this approach, not only to detect low-affinity complexes between small compounds and RNA, but also to provide information on their binding mode and on the way they can be connected. This NMR-spectroscopy-guided analysis enabled us to design micromolar ligands after the optimisation and connection of millimolar fragments with an appropriate linker. The influence of the linker region on the binding affinity and selectivity outlines the importance of having a flexible assemblage strategy with a variety of linkers in such an approach.
本文描述了一种基于片段的方法来合成HIV逆转录引物tRNA(Lys)(3)的配体。事实证明，核磁共振光谱法在这种方法中非常有用，它不仅能检测小分子化合物与RNA之间的低亲和力复合物，还能提供有关它们的结合模式以及连接方式的信息。这种由核磁共振光谱引导的分析使我们能够在将毫摩尔级片段与合适的连接子进行优化和连接后，设计出微摩尔级的配体。连接子区域对结合亲和力和选择性的影响凸显了在这种方法中采用具有多种连接子的灵活组装策略的重要性。
