Hepcidin analogues and uses thereof

A method of treating a disease of iron metabolism in a subject, comprising administering to the subject an effective amount of at least one peptide according to formula I′:

• (I′)
• (SEQ ID NO:
• 21)
• R1′-X′-Y′-R2′
• or a pharmaceutically acceptable salt thereof, wherein
• R1′ is hydrogen, a C1-C6 alkyl, a C6-C12 aryl, a C1-C20 alkanoyl or pGlu;
• R2′ is —NH2 or —OH;
• X′ is a peptide sequence having the formula Ia′
• (Ia′)
• (SEQ ID NO:
• 13)
• X1-X2-X3-X4-X5-X6-X7-X8-X9-X10
• wherein
• X1 is Asp, Ida, pGlu, bhAsp, or absent;
• X2 is Thr;
• X3 is His;
• X4 is Phe, or Dpa;
• X5 is Pro, or bhPro;
• X6 is Ile, Cys, or Arg;
• X7 is Cys, IIe, Leu, or Val;
• X8 is Ile, Arg, Phe, Gln, Lys, or Glu;
• X9 is Phe or bhPhe;
• and
• X10 is Lys, Phe or absent;
• wherein if Y′ is absent, X7 is Ile;
• and
• Y′ is a peptide sequence having the formula IIa′
• (IIa′)
• (SEQ ID NO:
• 16)
• Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15
• wherein
• Y1 is Gly, Cys, Ala, Phe, Pro, Glu, Lys, D-Pro, Val, Ser or absent;
• Y2 is Pro, Ala, Cys, Gly or absent;
• Y3 is Arg, Lys, Pro, Gly, His, Ala, Trp or absent;
• Y4 is Ser, Arg, Gly, Trp, Ala, His, Tyr or absent;
• Y5 is Lys, Met, Arg, Ala or absent;
• Y6 is Gly, Ser, Lys, IIe, Ala, Pro, Val or absent;
• Y7 is Trp, Lys, Gly, Ala, IIe, Val or absent;
• Y8 is Val, Thr, Gly, Cys, Met, Tyr, Ala, Glu, Lys, Asp, Arg or absent;
• Y9 is Cys, Tyr or absent;
• Y10 is Met, Lys, Arg, Tyr or absent;
• Y11 is Arg, Met, Cys, Lys or absent;
• Y12 is Arg, Lys, Ala or absent;
• Y13 is Arg, Cys, Lys, Val or absent;
• Y14 is Arg, Lys, Pro, Cys, Thr or absent;
• and
• Y15 is Thr, Arg or absent;
• wherein the peptide of formula I′ comprises two cysteine residues linked via a disulfide bond, wherein the peptide is optionally PEGylated on R1′, X′, or Y′;
• wherein a side chain of an amino acid of the peptide is optionally conjugated to a lipophilic substituent or a polymeric moiety;
• and
• wherein the disease of iron metabolism is hereditary hemochromatosis, iron hemochromatosis, HFE (human factors engineering) mutation hemochromatosis, hepcidin deficiency, transfusional iron overload, or thalassemia.