Testosterone-inducing peptide compounds and associated combinations
The present disclosure concerns peptide compounds of formula I or II and combinations thereof that can be administered orally for promoting endogenous steroid, and particularly testosterone, production: (I) A-Xaa 1 -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -Xaa 6 -Xaa 7 -Xaa 8 -B (II) A-Xaa 1 -Xaa A -Xaa B -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -Xaa 6 -Xaa 7 -Xaa C - Xaa D -Xaa E -Xaa 8 -B.
1. An isolated peptide consisting of formula I:
(I)
A-Xaa 1 -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -
Xaa 6 -Xaa 7 -Xaa 8 -B
wherein:
A is present or absent and is a moiety improving the circulation half-life of the isolated peptide;
Xaa 1 is present or absent, when present Xaa 1 is a L- or D-amino acid residue;
Xaa 2 is present or absent, when present Xaa 2 is a L-serine or D-serine;
Xaa 3 is a L-lysine, a D-lysine, a L-arginine or a D-arginine;
Xaa 4 is a L-valine, a D-valine, a L-isoleucine, a D-isoleucine, a L-leucine, a D-leucine, a glycine, a D-alanine or a L-alanine;
Xaa 5 is a L-serine, a D-serine, a L-threonine or a D-threonine;
Xaa 6 is a L-glutamine, a D-glutamine, a L-glutamic acid or a D-glutamic acid;
Xaa 7 is present or absent, when present Xaa 7 is a L-serine or a D-serine;
Xaa 8 is present or absent, when present Xaa 8 is a L- or D-amino acid residue; and
B is present or absent and is a moiety improving the circulation half-life of the isolated peptide, wherein A and B are not a peptide.
2. The isolated peptide of claim 1 in which Xaa 1 is absent and/or Xaa 2 is absent.
3. The isolated peptide of claim 1 , in which Xaa 3 -Xaa 4 -Xaa 5 -Xaa 6 -Xaa 7 has the amino acid sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22 or 23.
4. The isolated peptide of claim 1 , in which Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -Xaa 6 -Xaa 7 has the amino acid sequence of SEQ ID NO: 16 or 23.
5. The isolated peptide of claim 1 , in which Xaa 3 is L- or D-lysine.
6. The isolated peptide of claim 1 , in which Xaa 3 is L- or D-arginine.
7. The isolated peptide of claim 1 , in which Xaa 4 is L-valine or D-valine.
8. The isolated peptide of claim 1 , in which Xaa 4 is L-isoleucine or D-isoleucine.
9. The isolated peptide of claim 1 , in which Xaa 4 is L-leucine or D-leucine.
10. The isolated peptide of claim 1 , in which Xaa 5 is L-serine or D-serine.
11. The isolated peptide of claim 1 , in which Xaa 5 is L-threonine or D-threonine.
12. The isolated peptide of claim 1 , in which Xaa 6 is L-glutamine or D-glutamine.
13. The isolated peptide of claim 1 , in which Xaa 6 is L-glutamic acid or D-glutamic acid.
14. The isolated peptide of claim 1 , in which Xaa 7 is absent.
15. The isolated peptide of claim 1 , in which Xaa 7 is present.
16. The isolated peptide of claim 1 , in which Xaa 8 is absent.
17. The isolated peptide of claim 1 , wherein A is an acetyl cap or a polyethylene glycol.
18. The isolated peptide of claim 1 , wherein B is an amide cap.
19. A peptide compound of formula II:
(II)
A-Xaa 1 -Xaa A -Xaa B -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 -
Xaa 6 -Xaa 7 -Xaa C -Xaa D -Xaa E -Xaa 8 -B
wherein:
A is present or absent and is a moiety improving the circulation half-life of the peptide compound;
Xaa 1 is present or absent, when present Xaa 1 is a L- or D-amino acid residue;
Xaa A is present or absent, when present Xaa A is a L-serine or D-serine;
Xaa B is present or absent, when present Xaa B is a L-lysine or D-lysine;
Xaa 2 is present or absent, when present Xaa 2 is a L-serine or D-serine;
Xaa 3 is a L-lysine, a D-lysine, a L-arginine or a D-arginine;
Xaa 4 is a L-valine, a D-valine, a L-isoleucine, a D-isoleucine, a L-leucine, a D-leucine, a glycine, a D-alanine or a L-alanine;
Xaa 5 is a L-serine, a D-serine, a L-threonine or a D-threonine;
Xaa 6 is a L-glutamine, a D-glutamine, a L-glutamic acid or a D-glutamic acid;
Xaa 7 is present or absent, when present Xaa 7 is a L-serine or a D-serine;
Xaa C is present or absent, when present Xaa C is a L-asparagine or D-asparagine;
Xaa D is present or absent, when present Xaa D is a L-phenylalanine or D-phenylalanine;
Xaa E is present or absent, when present Xaa E is a L-alanine or D-alanine;
Xaa 8 is present or absent, when present Xaa 8 is a L- or D-amino acid residue; and
B is present or absent and is a moiety improving the circulation half-life of the isolated peptide, wherein A and B are not a peptide.
20. A method for promoting the endogenous production of testosterone in a cell, said method comprising contacting the cell with at least one of:
the isolated peptide of claim 1
so as to promote the endogenous production of testosterone in the cell.