Author/Authors :
Dongmei Han، نويسنده , , F. Holger F?rsterling، نويسنده , , Xiaoyan Li، نويسنده , , Jeffrey R. Deschamps، نويسنده , , Damon Parrish، نويسنده , , Hui Cao، نويسنده , , Sundari Rallapalli، نويسنده , , Terry Clayton، نويسنده , , Yun Teng، نويسنده , , Samarpan Majumder، نويسنده , , Subramaniam Sankar، نويسنده , , Bryan L. Roth، نويسنده , , Werner Sieghart، نويسنده , , Roman Furtmüller، نويسنده , , James K. Rowlett، نويسنده , , Michael R. Weed، نويسنده , , James M. Cook، نويسنده ,
Abstract :
The stable conformations of GABAA–benzodiazepine receptor bivalent ligands were determined by low temperature NMR spectroscopy and confirmed by single crystal X-ray analysis. The stable conformations in solution correlated well with those in the solid state. The linear conformation was important for these dimers to access the binding site and exhibit potent in vitro affinity and was illustrated for α5 subtype selective ligands. Bivalent ligands with an oxygen-containing linker folded back upon themselves both in solution and the solid state. Dimers which are folded do not bind to Bz receptors.
Keywords :
conformation , Benzodiazepines , NMR , GABA
