| Abstract
| - The substituted thieno[2,3-d]pyrimidine 3 (Org 41841), a partial agonist for the luteinizing hormone/choriogonadotropin receptor (LHCGR) and the closely related thyroid-stimulating hormone receptor (TSHR),was fundamentally altered, and the resulting analogues were analyzed for their potencies, efficacies, andspecificities at LHCGR and TSHR. Chemical modification of the parent compound combined with priormutagenesis of TSHR provided compelling experimental evidence in support of computational models of3 binding to TSHR and LHCGR within their transmembrane cores. Biochemical analysis of a specificmodification to the chemical structure of 3 provides additional evidence of a H-bond between the ligandand a glutamate residue in transmembrane helix 3, which is conserved in both receptors. Several keyinteractions were surveyed to determine their respective biochemical roles in terms of both van der Waalsdimensions and hydrogen bond capacity and the respective relationship to biological activity.
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