Synthesis and evaluation of homodimeric GnRHR antagonists having a rigid bis-propargylated benzene core
| Autor: | Annemiek D. Knijnenburg, Richard J. B. H. N. van den Berg, Julia Oosterom, Laura H. Heitman, Gijsbert A. van der Marel, Cornelis Marius Timmers, Kimberly M. Bonger, Ad P. IJzerman, Herman S. Overkleeft |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cell Survival
Stereochemistry Dimer Clinical Biochemistry Allosteric regulation Pharmaceutical Science CHO Cells Ligands Biochemistry Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Cricetulus Cricetinae Drug Discovery Animals Humans Structure–activity relationship Amino Acids Databases Protein Molecular Biology G protein-coupled receptor Molecular Structure Ligand Organic Chemistry GNRHR Benzene Iodides Pargyline chemistry Molecular Medicine Dimerization Receptors LHRH Gonadotropin-releasing hormone receptor |
| Zdroj: | Bioorganic & Medicinal Chemistry. 16:3744-3758 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2008.01.054 |
| Popis: | The fact that GPCRs might function in a dimeric fashion is currently well accepted. For GnRHR, a GPCR that regulates gonadotropin release, there is evidence that the receptor also functions as a dimer. We here describe the design and synthesis of a set of dimeric GnRHR antagonists in order to understand the interaction of dimeric ligands to the receptor and to address the question whether GnRHR dimerization is a prerequisite for signalling. Biological evaluation of the compounds shows no discrimination between monomeric and dimeric-ligands in respect to binding affinities, however, the dimeric ligands appear to have different functional properties. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect