In:
ChemMedChem, Wiley, Vol. 4, No. 7 ( 2009-07-06), p. 1189-1195
Abstract:
Two series of dimeric ligands for a G‐protein‐coupled receptor were prepared that differ by the interconnecting spacer system. Biological evaluation revealed that both dimeric series exhibit unique biological properties relative to their monomeric counterparts. magnified image The luteinizing hormone receptor (LHR), the follicle‐stimulating hormone receptor (FSHR), and the thyroid‐stimulating hormone receptor (TSHR) belong to the glycoprotein hormone receptor (GpHR) family. A prominent feature of all endogenous glycoprotein ligands is that they share an identical α subunit and acquire their selectivity from the unique β subunit. Recent developments in pro‐fertility research have led to the discovery of several low‐molecular‐weight agonists for the luteinizing hormone/choriogonadotropin receptor that bind to the transmembrane (TM) region of the LHR. Interestingly, some of these agonists are also able to activate the FSHR. Several research groups have shown that ligand dimerization presents a powerful tool to increase the subtype selectivity for structurally related G‐protein‐coupled receptors. In this work, we applied the dimerization strategy to GpHRs and explored the effect on receptors with closely related TM regions. Two series of dimeric ligands were prepared that differ in the interconnecting spacer system. Biological evaluation revealed that both series exhibit unique selectivity properties for the LHR, originating from either decreased potency or a decreased efficacy toward the FSHR.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.200900058
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2209649-8
SSG:
15,3
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