Modified mini-hepcidin peptides and methods of using thereof
Disclosed herein are peptides which exhibit hepcidin activity and methods of making and using thereof.
1. A peptide comprising the following amino acid sequence:
Ida-T-H-Dpa-bhPro-R—C-R-bhPhe-Ahx-Ida(NHPal) (SEQ ID NO: 94) wherein
Ida is 2,2′-azanediyldiacetic acid;
Dpa is 3,3-diphenyl-L-alanine;
bhPro is L-β-homoproline;
bhPhe is (S)-2-amino-4-phenylbutanoic acid;
Ahx is an aminohexanoic acid spacer; and
Ida(NHPal) is 2,2′-azanediyldiacetic acid having a palmitylamine amide on the side chain.
2. A composition comprising at least one peptide according to claim 1 .
3. The composition according to claim 2 , wherein the composition is a pharmaceutical composition.
4. A kit comprising at least one peptide according to claim 1 packaged together with a reagent, a device, instructional material, or a combination thereof.
5. A complex comprising the peptide according to claim 1 bound to a ferroportin or an antibody.
6. A method of binding a ferroportin or inducing ferroportin internalization and degradation which comprises contacting the ferroportin with the peptide according to claim 1 .
7. A method of treating a disease of iron metabolism in a subject which comprises administering at least one peptide according to claim 1 to the subject.
8. The method of claim 7 , wherein the disease of iron metabolism is an iron overload disease.
9. The method of claim 7 , wherein the at least one peptide is administered at an effective daily dose as a single daily dose or as divided daily doses.
10. The method of claim 9 , wherein the effective daily dose is about 10-500 μg/kg/day and the at least one peptide is provided in a formulation for subcutaneous injection.
11. The method of claim 9 , wherein the effective daily dose is about 10-1000 μg/kg/day and the at least one peptide is provided in a formulation for oral, pulmonary, or mucosal administration.
12. A peptide consisting of the following amino acid sequence:
Ida-T-H-Dpa-bhPro-R-C-R-bhPhe-Ahx-Ida(NHPal) (SEQ ID NO: 94) wherein
Ida is 2,2′-azanediyldiacetic acid;
Dpa is 3,3-diphenyl-L-alanine;
bhPro is L-β-homoproline;
bhPhe is (S)-2-amino-4-phenylbutanoic acid;
Ahx is an aminohexanoic acid spacer; and
Ida(NHPal) is 2,2′-azanediyldiacetic acid having a palmitylamine amide on the side chain.
13. A composition which comprises the peptide according to claim 12 .
14. The composition according to claim 13 , wherein the composition is a pharmaceutical composition.
15. A kit comprising the peptide according to claim 12 packaged together with a reagent, a device, instructional material, or a combination thereof.
16. A complex comprising the peptide according to claim 12 bound to a ferroportin or an antibody.
17. A method of binding a ferroportin or inducing ferroportin internalization and degradation which comprises contacting the ferroportin with the peptide according to claim 12 .
18. A method of treating a disease of iron metabolism in a subject which comprises administering the peptide according to claim 12 to the subject.
19. The method of claim 18 , wherein the disease of iron metabolism is an iron overload disease.
20. The method of claim 18 , wherein the peptide is administered at an effective daily dose as a single daily dose or as divided daily doses.
21. The method of claim 20 , wherein the effective daily dose is about 10-500 μg/kg/day and the peptide is provided in a formulation for subcutaneous injection.
22. The method of claim 20 , wherein the effective daily dose is about 10-1000 μg/kg/day and the peptide is provided in a formulation for oral, pulmonary, or mucosal administration.