1032418-05-5Relevant articles and documents
Synthesis and evaluation of homodimeric GnRHR antagonists having a rigid bis-propargylated benzene core
Bonger, Kimberly M.,van den Berg, Richard J.B.H.N.,Knijnenburg, Annemiek D.,Heitman, Laura H.,IJzerman, Ad P.,Oosterom, Julia,Timmers, Cornelis M.,Overkleeft, Herman S.,van der Marel, Gijsbert A.
, p. 3744 - 3758 (2008/12/21)
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.
