85888-68-2Relevant articles and documents
Design of tRNALys3 Ligands: Fragment evolution and linker selection guided by NMR spectroscopy
Chung, Florence,Tisne, Carine,Lecourt, Thomas,Seijo, Bili,Dardel, Frederic,Micouin, Laurent
scheme or table, p. 7108 - 7116 (2010/04/05)
A fragment-based approach for the synthesis of ligands of tRNA Lys3, 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 lowaffinity 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. 2009 Wiley-VCH Verlag GmbH & Co. KGaA.