Determination of the binding mode of thienopyrimidinedione antagonists to the human gonadotropin releasing hormone receptor using structure-activity relationships, site-directed mutagenesis, and homology modeling.

@article{Betz2006DeterminationOT,
  title={Determination of the binding mode of thienopyrimidinedione antagonists to the human gonadotropin releasing hormone receptor using structure-activity relationships, site-directed mutagenesis, and homology modeling.},
  author={Stephen F. Betz and Francisco M. Lio and Yinghong Gao and Greg J Reinhart and Zhiqiang Guo and Michael F. Mesleh and Y Zhu and Raymond Struthers},
  journal={Journal of medicinal chemistry},
  year={2006},
  volume={49 21},
  pages={6170-6}
}
We have investigated the specific interactions of a series thienopyrimidinediones with the gonadotropin-releasing hormone receptor (GnRH-R). Competitive radioligand binding assays were used to determine the effect of several mutants on nonpeptide binding. Distinct interactions were observed in two separate regions: the N-terminal end of TM7 and the C-terminal end of TM6. The effects of mutants at D302((7.32)) and H306((7.36)) suggest that these residues are part of a hydrogen-bond network… CONTINUE READING