Characterization of Peptide 20–30 of Follicle Stimulating Hormone Receptor as an Antagonist of Receptor Activity: Significance of Charged Residues

We had previously reported the region (20–30) from follicle stimulating hormone receptor as being an immunodominant epitope and the smallest reported peptide capable of inhibiting hormone binding. We now report it to be an effective antagonist of ligand‐induced cAMP signalling as well. The region (20–30) of follicle stimulating hormone receptor has three charged residues, namely, E²², D²⁶ and R²⁹ that are specific to follicle stimulating hormone receptor and are conserved in mammals. This study aimed to verify whether the charged residues contribute to the activity of the follicle stimulating hormone receptor peptide (20–30). This was done using analogs of follicle stimulating hormone receptor peptide (20–30), each having an alanine substitution for a corresponding charged residue. The analog peptides displayed a loss of activity and could not inhibit hormone binding or the subsequent signal transduction. The ability of follicle stimulating hormone receptor peptide (20–30) to bind antipeptide antibodies against follicle stimulating hormone receptor peptide (9–30) was either decreased or abolished with the alanine substituted analog peptides of follicle stimulating hormone receptor peptide (20–30). The loss of function led us to verify whether there was a conformational change as well. CD spectral analysis did not reveal a significant change. These observations indicate that the charged aminoacids present in follicle stimulating hormone receptor peptide (20–30) are crucial for the observed follicle stimulating hormone antagonistic activity. This information could form the basis for the design of novel compounds capable of functioning as follicle stimulating hormone antagonists.