Diuretic peptide conjugate
Disclosed are a variety of peptide conjugates represented by the following general formula: R 1 -Z-X-Z′-R 2 including methods of making and using such conjugates. Also provided are antibodies that specifically bind the peptide conjugates. The present invention has a wide spectrum of important applications including use in the treatment of disorders impacted by nociceptin and related opioid-like peptides.
1. A peptide conjugate having the following formula:
R 1 -Arg-Tyr-Tyr-Arg-Trp-Lys-Lys-Lys-Lys-Lys-Lys-Lys-R 2 ,
wherein R 1 represents hydrogen, acyl, acetyl, or a trifluoroacetyl group and R 2 represents hydroxyl or NR 3 R 4 in which each of R 3 and R 4 independently represents hydrogen, C(1-6) alkoxy, C(1-6) aryloxy, or C(1-6) lower alkyl; and a salt, hydrate, or a solvate thereof.
2. A solution comprising a peptide conjugate having the following formula:
R 1 -Arg-Tyr-Tyr-Arg-Trp-Lys-Lys-Lys-Lys-Lys-Lys-Lys-R 2 ,
wherein R 1 represents hydrogen, acyl, acetyl, or a trifluoroacetyl group and R 2 represents hydroxyl or NR 3 R 4 in which each of R 3 and R 4 independently represents hydrogen, C(1-6) alkoxy, C(1-6) aryloxy, or C(1-6) lower alkyl; and a salt, hydrate, or a solvate thereof, wherein the solution is sterile.
3. A peptide conjugate having the following formula:
Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-Lys-Lys-Lys-Lys-Lys-Lys-NH 2 ; and a salt, hydrate, or a solvate thereof.
4. A solution comprising a peptide conjugate having the following formula:
Ac-Arg-Tyr-Tyr-Arg-Trp-Lys-Lys-Lys-Lys-Lys-Lys-Lys-NH 2 ; and a salt, hydrate, or a solvate thereof, wherein the solution is sterile.
5. A composition comprising a peptide conjugate having the following formula:
R 1 -Arg-Tyr-Tyr-Arg-Trp-Lys-Lys-Lys-Lys-Lys-Lys-Lys-R 2 , wherein R 1 represents hydrogen, acyl, acetyl, or a trifluoroacetyl group and R 2 represents hydroxyl or NR 3 R 4 in which each of R 3 and R 4 independently represents hydrogen, C(1-6) alkoxy, C(1-6) aryloxy, or C(1-6) lower alkyl; and a salt, hydrate, or a solvate thereof, the composition further comprising a pharmaceutically acceptable carrier or diluent.
6. The composition of claim 5 , wherein the pharmaceutically acceptable carrier is a solid, the composition being in a tablet form.
7. The composition of claim 5 , wherein the diluent is a liquid comprising isotonic saline.
8. A peptide conjugate having the following formula:
R 1 -Arg-Tyr-Tyr-Arg-Trp-Z-R 2 , wherein R 1 represents hydrogen, acyl, acetyl, or a trifluoroacetyl group, Z represents (Lys) 11 , (Lys) 10 , (Lys) 9 , (Lys) 8 , (Lys) 6 , or (Lys) 5 and R 2 represents hydroxyl or NR 3 R 4 in which each of R 3 and R 4 independently represents hydrogen, C(1-6) alkoxy, C(1-6) aryloxy, or C(1-6) lower alkyl; and a salt, hydrate, or a solvate thereof.
9. A composition comprising a peptide conjugate having the following formula:
R 1 -Arg-Tyr-Tyr-Arg-Trp-Z-R 2 , wherein R 1 represents hydrogen, acyl, acetyl, or a trifluoroacetyl group, Z represents (Lys) 11 , (Lys) 10 , (Lys) 9 , (Lys) 8 , (Lys) 6 , (Lys) 5 and R 2 represents hydroxyl or NR 3 R 4 in which each of R 3 and R 4 independently represents hydrogen, C(1-6) alkoxy, C(1-6) aryloxy, or C(1-6) lower alkyl; and a salt, hydrate, or a solvate thereof.
10. The composition of claim 9 , wherein the composition further comprises a pharmaceutically acceptable carrier or diluent.
11. The composition of claim 10 , wherein the pharmaceutically acceptable carrier is a solid, the composition being in a tablet form.
12. The composition of claim 10 , wherein the pharmaceutically acceptable carrier is a liquid comprising isotonic saline.
13. A solution comprising a peptide conjugate having the following formula:
R 1 -Arg-Try-Tyr-Arg-Trp-Z-R 2 ,
wherein, R 1 represents hydrogen, acyl, acetyl, or a trifluoroacetyl group, Z represents (Lys) 11 , (Lys) 10 , (Lys) 9 , (Lys) 8 , (Lys) 6 , or (Lys) 5 and R 2 represents hydroxyl or NR 3 R 4 in which each of R 3 and R 4 independently represents hydrogen, C(1-6) alkoxy, C(1-6) aryloxy, or C(1-6) lower alkyl; and a salt, hydrate, or a solvate thereof, wherein the solution is sterile.
14. A peptide conjugate having the following formula:
Ac-Arg-Tyr-Tyr-Arg-Trp-Z-NH 2 , wherein, Z represents (Lys) 11 , (Lys) 10 , (Lys) 9 , (Lys) 8 , (Lys) 6 , or (Lys) 5 and a salt, hydrate, or a solvate thereof.
15. A composition comprising a peptide conjugate having the following formula:
Ac-Arg-Tyr-Tyr-Arg-Trp-Z-NH 2 , wherein, Z represents (Lys) 11 , (Lys) 10 , (Lys) 9 , (Lys) 8 , (Lys) 6 , (Lys) 5 ; and a salt, hydrate, or a solvate thereof.
16. The composition of claim 15 , wherein the composition further comprises a pharmaceutically acceptable carrier or diluent.
17. The composition of claim 16 , wherein the pharmaceutically acceptable carrier is a solid, the composition being in a tablet form.
18. The composition of claim 16 , wherein the diluent is a liquid comprising isotonic saline.
19. A solution comprising a peptide conjugate having the following formula:
Ac-Arg-Tyr-Tyr-Arg-Trp-Z-NH 2 , wherein, Z represents (Lys) 11 , (Lys) 10 , (Lys) 9 , (Lys) 8 , (Lys) 6 , (Lys) 5 ; and a salt, hydrate, or a solvate thereof, wherein the solution is sterile.