NON-MAMMALIAN GnRH ANALOGS AND USES THEREOF IN REGULATION OF FERTILITY AND PREGNANCY

摘要

Specially designed non-mammalian GnRH analog decapeptides resistant to degradation by the placental enzyme, C-ase-1, or a post-proline peptidase, are disclosed. The GnRH analogs are further defined as analogs of Chicken II GnRH or Salmon GnRH. These non-mammalian analogs incorporate D-arginine, D-leucine, D-tBu-Serine or D-Trp at position 6 and ethylamide or aza-Gly-amide at position 10. The D-Arg (6) - Chicken II GnRH - ethylamide, D-Arg (6) - Chicken II GnRH-aza-Gly (10)-amide, the D-Arg (6) - Salmon GnRH ethylamide, and D-Arg (6) - Salmon GnRH-aza-Gly (10)-amide analogs are also provided, and demonstrate preferential binding to chorionic GnRH receptor that is greater relative to the binding of these analogs to pituitary GnRH receptor. These non-mammalian GnRH analogs may be used in pharmaceutical preparations, and specifically in various treatment methods as a contraceptive or post-coital contraceptive agent. The non-mammalian GnRH analogs are also provided in pharmaceutical preparations that may be used clinically for maintaining pregnancy when used in very low doses and administered in pulsatile fashion. In another aspect, the non-mammalian GnRH analogs may be used as luteolytic agents. The aza-Gly (10) amide non-mammalian analogs are yet other embodiments of the non-mammalian GnRH analogs provided as a part of the invention.