The Salk Institute for Biological Studies

Guangcheng Jiang

Jean E Rivier

Catherine L Rivier

John S Porter

Carl A Hoeger

Betides having at least one betidamino acid are provided which have GnRH antagonistic properties. These antagonists may be used to regulate fertility and to treat steroid-dependent tumors, such as prostatic and mammary tumors. One particularly effective betide, which is an analog of the decapeptide GnRH that is highly soluble in water at physiologic pH, has the formula: Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-Aph(acetyl)-D-Aph(acetyl)-Leu-D/L-Agl(methyl,i sopropyl .beta.-alanyl)-Pro-D-Ala-NH.sub.2, and another has the formula Ac-D-2Nal-D-Cpa-D-3Pal-D/L-Agl(For)-Aph(Ac)-D-Aph(Ac)-Leu-ILys-Pro-D-Ala-N H.sub.2.

GNRH antagonist betides

Analogs of the decapeptide GnRH which include two significantly modified amino acids at positions 5 and 6 inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads and may be used to treat steroid-dependent tumors. Particularly effective peptides which are soluble in water at physiologic pH and which have a low tendency to gel when administered in vivo have the following formula:

Growing community of inventors

La Jolla, CA, United States of America

Guangcheng Jiang