1.Potent GnRH agonists containing L-amino acid derivatives in the six position.
Seprödi J, Erchegyi J, Vadász Z, Teplán I, Mezö I, Kanyicska B, Kovács M, Vigh S. Biochem Biophys Res Commun. 1987 May 14;144(3):1214-21.
New agonists related to gonadotropin-releasing hormone (GnRH) have been synthesized that are comparable in potency to the GnRH and its superagonists for release of LH and estrus suppression without substitutions with D- or unnatural amino acids in position 6. We now report a series of L-beta-aspartyl-6 GnRH analogs containing only naturally occurring L-amino acids in the whole sequence, exhibiting considerable in vivo biological activity. Dose and time dependent LH release capability of the different analogs in adult male mice, estrus suppression comparisons and blockade of ovulation in female rats are given. The incorporation of L-Asp-OMe and L-Asp-OBzl in position 6 of GnRH resulted in the most potent GnRH agonists (to 12-20xGnRH potency) in this series inducing a biphasic biological response similar to the D-amino acid-6 substituted superactive GnRH analogs. A correlation between the LH releasing potencies of the analogs and their HPLC retention times was also investigated.
