[Des-Gly10]-LH-RH ethylamide, a nonapeptide closely related to LH-RH, has about two and one-half times the luteinizing hormone releasing activity and a comparable FSH releasing activity to the natural hormone when assayed in vivo. In addition to being enhanced, the LH-RH-FSH-RH activity was prolonged. In an effort to produce competitive inhibitors of LH-RH, the [des-His2,des-Gly10]- and [des-Trp3, des-Gly10]-LH-RH ethylamides were prepared. The peptides, as well as [des-Gly10]-LH-RH ethylamide, were synthesized by the solid-phase method via protected peptides which were cleaved from the solid support by treatment with ethylamine. Protecting groups were then eliminated by reaction with hydrogen fluoride, to give peptides which were purified by column chromatography. Both compounds exhibited virtually no LH or FSH releasing activity in vivo. However, the [des-His2] peptide was a potent inhibitor of LH-RH in vivo whereas the [des-Trp3] analog showed little antagonist activity.
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