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US 6,284,732 B1Granted
Peptides and peptide analogues designed from HFE protein and their uses in the treatment of iron overload diseases
AssigneeBio-Rad Laboratories, Inc.
InventorsJohn N. Feder, Randall C. Schatzman, Pamela J. Bjorkman, Melanie Bennett, Jose Lebron
Life of this patent
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Abstract
The present invention relates to peptides and peptide analogues designed from HFE protein. In particular, it relates to peptides and peptide analogues designed from an alpha-1 region of HFE protein which lowers the binding affinity of transferrin receptor for transferrin. Such compounds mimic HFE protein function, and reduce iron uptake and/or accumulation by a cell.
Claims7
A compound comprising the formula:
- Z1-X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-Z2 (I)
- wherein:
- X1 is an apolar residue;
- X2 is a hydrophobic residue;
- X3 is an acidic or an aliphatic residue;
- X4 is a basic residue;
- X5 is an apolar residue;
- X6 is an aromatic residue;
- X7 is a polar residue;
- X8 is an aliphatic residue;
- X9 is an acidic or an aliphatic residue;
- X10 is an aromatic residue;
- X11 is an aromatic residue;
- X12 is a polar residue;
- X13 is Ile;
- X14 is an apolar residue;
- X15 is an acidic residue;
- X16 is a polar residue;
- X17 is a basic or an aliphatic residue;
- Z1 is H2N—, RHN— or, RRN—;
- Z2 is —C(O)R, —C(O)OR, —C(O)NHR, —C(O)NRR;
- each R is independently (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkynyl, substituted (C1-C6) alkyl, substituted (C1-C6) alkenyl or substituted (C1-C6) alkynyl;
- each “-” between residues Z1 and X1 and residues Z2 and X17 represents a covalent linkage;
- and
- each “-” between residues X1 through X17 represents a covalent linkage wherein the compound reduces cell-associated binding of transferrin as measured in an in vitro cellular binding assay and produces at least an additive effect with soluble HFE/β2m heterodimers in reducing cell associated binding of transferrin as measured in the assay.
22 more elements
A composition comprising a acceptable carrier, excipient or diluent and a compound according to formula (II):
- Z1-X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-Z2 (II)
- wherein:
- X1 is an apolar residue;
- X2 is a hydrophobic residue:
- X3 is an acidic or an aliphatic residue;
- X4 is a basic residue;
- X5 is an apolar residue;
- X6 is an aromatic residue;
- X7 is a polar residue:
- X8 is an aliphatic residue;
- X9 is an acidic or an aliphatic residue;
- X10 is an aromatic residue;
- X11 is an aromatic residue;
- X12 is a polar residue;
- X13 is Ile;
- X14 is an apolar residue;
- X15 is an acidic residue;
- X16 is a polar residue;
- X17 is a basic or an aliphatic residue;
- Z1 is H2N—, RHN— or, RRN—;
- Z2 is —C(O)R, —C(O)OR, —C(O)NHR, —C(O)NRR;
- each R is independently (C1-C6) alky, (C1-C6) alkenyl, (C1-C6) alkynyl, substituted (C1-C6) alkyl, substituted (C1-C6) alkenyl or substituted (C1-C6) alkynyl;
- each “-” between residues Z1 and X1 and residues Z2 and X17 represents a covalent linkage;
- and
- each “-” between residues X1 through X17 represents a covalent linkage, wherein the compound reduces cell-associated binding of transferrin as measured in an in vitro cellular binding assay and produces at least an additive effect with soluble HFE/β2m heterodimers in reducing cell-associated binding of transferrin as measured in the assay.
22 more elements
Dependencies are inferred from the claim text.