DNA coding for polypeptide fusion
A hybrid protein includes two coexpressed amino acid sequences forming a dimer. Each sequence contains the binding portion of a receptor, such as TBP1 or TBP2, or a ligand, such as IL-6, IFN-β and TPO, linked to a subunit of a natural heterodimeric scaffold. Each coexpressed sequence contains a corresponding subunit so as to form a heterodimer upon expression. Corresponding DNA molecules, expression vectors and host cells are also disclosed as are pharmaceutical compositions and a method of producing such proteins.
1 . An isolated DNA molecule coding for a sequence (a) fused to a sequence (b), wherein:
sequence (a) is at least one amino acid sequence selected from the group consisting of a chain of a homomeric receptor, a chain of a heteromeric receptor, a ligand other than a gonadotropin, and a fragment of said chain of said homomeric receptor, said chain of said heteromeric receptor or said ligand, wherein said ligand or fragment thereof retains ligand-receptor binding capability and said chain of said homomeric receptor or fragment thereof and said chain of said heteromeric receptor or fragment thereof retain ligand-receptor binding capability either alone or in association with a homologous or heterologous chain of said receptor; and
sequence (b) is a subunit of a heterodimeric proteinaceous hormone, or a fragment thereof which retains the ability of the subunit to form a heterodimer with other subunits thereof.
2 . The isolated DNA molecule of claim 1 , wherein the subunit of a heteromeric proteinaceous hormone, or a fragment thereof, in sequence (b) is from a heteromeric proteinaceous hormone selected from the group consisting of hCG, FSH, LH, TSH, inhibin or fragments thereof.
3 . The isolated DNA molecule of claim 1 , wherein the subunit of a heteromeric proteinaceous hormone, or a fragment thereof, in sequence (b) is from a gonadotropin hormone.
4 . The isolated DNA molecule of claim 1 , wherein the subunit of a heteromeric proteinaceous hormone, or a fragment thereof, in sequence (b) is from hCG.
5 . The isolated DNA molecule of claim 1 , wherein said sequence (a) is the amino acid sequence of a ligand other than a gonadotropin.
6 . An isolated plasmid containing the DNA molecule of claim 1 .
7 . An isolated host cell transformed with the plasmid of claim 6 .