Fusion proteins of collagen-binding domain and parathyroid hormone

摘要

Fusion proteins containing active agonist or antagonist fragments of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP) coupled to a collagen-binding domain are presented. The fusion proteins can be used to promote bone growth, to promote hair growth, to prevent cancer metastasis to bone, to promote immune reconstitution with a bone marrow stem cell transplant, to promote mobilization of bone marrow stem cells for collection for autologous stem cell transplant, and to treat renal osteodystrophy. Pharmaceutical agents comprising a collagen-binding polypeptide segment linked to a non-peptidyl PTH/PTHrP receptor agonist or antagonist are also presented.

主权项

1. A composition comprising:
a collagen-binding polypeptide segment covalently linked to a PTH/PTHrP receptor antagonist; wherein the collagen-binding polypeptide segment is a ColH or ColG bacterial collagen binding polypeptide segment or a segment of a collagenase, wherein the PTH/PTHrP receptor antagonist comprises a peptide selected from the group consisting of residues 7-14 of SFQ ID NO: 7, residues 7-33 of SEQ ID NO: 7, residues 7-34 of SEQ ID NO: 7, residues 7-34 of SEQ ID NO: 8, and SEQ ID NO: 11, wherein the collagen-binding polypeptide segment comprises residues 38-158 of SEQ ID NO: 1, a fragment of at least 8 consecutive amino acids from residues 38-158 of SEQ ID NO: 1 or is at least 90% identical to residues 38-158 of SEQ ID NO: 1.