Peptides affecting gonadal function
AssigneeThe Salk Institute for Biological Studies
InventorsJean E. F. Rivier, Wylie W. Vale, Jr.
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Abstract
LRF analogs having a modified D-Phe residue in the 6-position act as superagonists exhibiting potencies many times more than that of LRF. The peptides or their nontoxic salts can be administered by intravenous, subcutaneous, sublingual, oral, intravaginal, intranasal or rectal routes. The peptides can be used to regulate fertility in male and female mammals, including human beings. The peptides are represented by the following formula: p-Glu-His-Trp-Ser-Ty-R.sub.1 -Leu-Arg-Pro-NH-CH.sub.2 -CH.sub.3 wherein R.sub.1 is selected from the group consisting of methyl-D-Phe, nitro-D-Phe, and methyoxy-D-Phe.
Claims8
A compound selected from the class defined by the formula:
- p-Glu-His-Trp-Ser-Tyr-R.sub.1 -Leu-Arg-Pro-NH-CH.sub.2 -CH.sub.3
- and its nontoxic salts, and
- X.sup.1 -p-Glu-His(X.sup.2)-Trp-Ser(X.sup.3)-Tyr-(X.sup.4)-R.sub.1 -Leu-Arg(X.sup.5)-Pro-X.sup.6
- wherein R.sub.1 is selected from the group consisting of methyl-D-Phe, nitro-D-Phe and methoxy-D-Phe;
- X.sup.1 is either hydrogen or an .alpha.-amino protecting group;
- X.sup.2 is a protecting group for the imidazole nitrogen atom selected from the group consisting of Tos, benzyl, trityl, 2,2,2-trifluoro-1-benzyloxycarbonylaminoethyl, 2,2,2-trifluoro-1-tert-butyloxycarbonylaminoethyl and 2,4-dinitrothiophenyl;
- X.sup.3 is a protecting group for the alcoholic hydroxyl group of Ser selected from the group consisting of acetyl, benzoyl, tetrahydropyranyl, tert-butyl, trityl, benzyl and 2,6-dichlorobenzyl;
- X.sup.4 is a protecting group for the phenolic hydroxyl group of Tyr selected from the group consisting of tetrahydropyranyl, tert-butyl, trityl, benzyl, benzyloxycarbonyl, 4-bromobenzyloxycarbonyl and 2,6-dichlorobenzyl;
- X.sup.5 is a protecting group for the nitrogen atoms of Arg selected from the group consisting of nitro, Tos, benzyloxycarbonyl, adamantyloxycarbonyl, and BOC, or is hydrogen;
- and X.sup.6 is selected from the group consisting of ethylamine, and O--CH.sub.2 --[resin support].
A method for regulating fertility and the production of gonadotropins and sex steroids in male and female mammalians comprising administering an effective amount of a peptide having the formula:
- p-Glu-His-Trp-Ser-Tyr-R.sub.1 -Leu-Arg-Pro-NH-CH.sub.2 -CH.sub.3
- wherein R.sub.1 is selected from the group consisting of methyl-D-Phe, nitro-D-Phe and methoxy-D-Phe.
Dependencies are inferred from the claim text.