KISS1R receptor agonist compounds and use thereof for inducing ovulation in mammals

1. A KISS1R receptor agonist peptide compound, selected from:

a pseudopeptide comprising the C-terminal sequence:

-Xaa1Ψ[Tz] Xaa2-Xaa3-Xaa4-NH 2   (SEQ ID NO: 3)

 wherein

W[Tz] represents a 1,4-disubstituted 1,2,3-triazole group of formula (I)

 replacing the peptide bond between the Xaa1 residue and the Xaa2 residue,

Xaa1 represents Gly or Ala,

Xaa2 represents Leu or an aliphatic α-aminoacyl analog residue,

Xaa3 represents Arg, the —NH 2 function of which is optionally substituted with a methyl group, or Xaa3 represents a positively charged α-aminoacyl analog residue, and

Xaa4 represents Tyr, Phe, Trp or an α-aminoacyl analog residue of aryl alanine type;

an analog of said pseudopeptide comprising the C-terminal sequence SEQ ID NO: 3, in which the amide peptide bond between Xaa2 and Xaa3 and/or between Xaa3 and Xaa4 is replaced with an isosteric bond;

or a salt of said pseudopeptide or said analog.

2. The peptide compound according to claim 1 , selected from:

the pseudopeptide of sequence:

Tyr-Asn-Trp-Asn-Ser-Phe-Xaa1Ψ[Tz]Xaa2-Xaa3-Xaa4-NH 2    (SEQ ID NO: 4);

an analog of said pseudopeptide capable of binding the KISS1R receptor;

or a salt of said pseudopeptide or said analog.

3. The peptide compound according to claim 2 , wherein the compound is the analog of said pseudopeptide of sequence SEQ ID NO: 4, in which at least one amino acid selected from Tyr1, Asn2 and Trp3 is replaced with a lysine (Lys).

4. The peptide compound according to claim 3 , wherein the amine function of said lysine is substituted with one or more groups selected from an alkanoyl group, a polyalkylene glycol chain, and a lipid chain.

5. The peptide compound according to claim 2 , wherein the compound is the analog of said pseudopeptide of sequence SEQ ID NO: 4, in which the amino acid Tyr1 is replaced with its D enantiomer.

6. The peptide compound according to claim 1 , wherein the N-terminal amine function is modified by substitution with a group selected from linear alkanoyls, a benzoyl group and a tetramethylguanidinium group.

7. The peptide compound according to claim 1 , wherein the N-terminal amine function is replaced with an azide function or with the 1,4-disubstituted 1,2,3-triazole group of formula (I).

8. The peptide compound according to claim 1 , wherein the N-terminal amine function is substituted with an alkyl group or with a benzyl group.

9. The peptide compound according to claim 8 , wherein said alkyl group is a linear alkyl.

10. The peptide compound according to claim 1 , wherein at least one amino acid is bonded to one or more polyalkylene glycol chains, one or more lipid chains, and/or one or more groups that bind to serum albumin.

11. The peptide compound according to claim 1 , wherein at least one amino acid is bonded to a group capable of binding to serum albumin.

12. The peptide compound according to claim 1 , wherein at least one amino acid is bonded to a γ-(N-hexadecanoyl-Glu-OH) group.

13. A pharmaceutical or veterinary composition, comprising the peptide compound according to claim 1 in a pharmaceutically acceptable carrier.

14. The composition according to claim 13 , in a form to be administered by intramuscular, subcutaneous, intravenous or intradermal injection, or in an orally administrable form.

15. A medicament, comprising the peptide compound according to claim 1 .

16. The medicament according to claim 15 , in a form to be administered as an injection.