| abstract |
Peptides which include unnatural amino acids and which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. The antagonists may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-position, the 5-position, the 6-position and/or the 8-position. Such unnatural amino acids are useful in the synthesis of peptides and have the formula U*: where n is an integer from 1 to 6; Y is N-CN, N-CONHR9?, S, O or CH-NO2?; R9? is H, Ac, lower alkyl, aromatic or heterocyclic; X is NH, O, S, M1?(CHq?)p?M2? or M1?-(CH2?)p'?-M2?(CH2?)p''?-M3?, where M1? is NR10?, O, S or CHR3? wherein R3? is methyl, ethyl, propyl, phenyl, pyridinyl, pyrimidinyl or purinyl; q is 1 or 2; p, p' and p'' are integers between 0 and 6; R10? is H, lower alkyl or the like, and M2? and M3? are M1?, COOH, CONH2?, COOR3? or CN; R1? is H, alkyl, modified alkyl, alkenyl, alkynyl, aryl or a direct bond to X; R2? is R1?, OH, NH2?, NHR1?, or heterocycle. |