Nucleic acids encoding interleukin-18 mutants
The invention provides mutants of IL-18 with lower affinity to IL-18BP than the wild type IL-18 molecule.
1. An isolated DNA encoding an interleukin-18 (IL-18) polypeptide comprising the amino acid sequence of SEQ ID NO: 2, except that one or more amino acid residues selected from the group consisting of Glu-42, Ile-85, Met-87, Lys-89, Met-96, Asp-130, Lys-132, Pro-143, Met-149, and Leu-189 are mutated.
2. The isolated DNA according to claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:3.
3. The isolated DNA according to claim 1 , wherein the polypeptide comprises the amino acid sequence of encoding the polypeptide of SEQ ID NO:4.
4. The isolated DNA according to claim 1 , wherein the polypeptide comprises the amino acid sequence of encoding the polypeptide of SEQ ID NO:5.
5. The isolated DNA according to claim 1 , wherein the polypeptide comprises the amino acid sequence of encoding the polypeptide of SEQ ID NO:6.
6. The isolated DNA according to claim 1 , wherein the polypeptide comprises the amino acid sequence of encoding the polypeptide of SEQ ID NO:7.
7. The isolated DNA according to claim 1 , wherein the polypeptide comprises the amino acid sequence of encoding the polypeptide of SEQ ID NO:8.
8. The isolated DNA according to claim 1 further comprising a nucleic acid molecule a signal peptide.
9. The isolated DNA according to claim 8 , wherein the signal peptide is that of a growth hormone.
10. A vector comprising the isolated DNA according to claim 1 , wherein said vector is capable of expressing the polypeptide encoded by said isolated nucleic acid in an appropriate host cell.
11. The vector according to claim 10 , wherein the host cell is prokaryotic.
12. The vector according to claim 11 , wherein the DNA encodes a polypeptide selected from a group consisting of SEQ ID NO:3, SEQ ID NO:4 and SEQ ID NO:5.
13. The vector according to claim 10 , wherein the host cell is a eukaryotic cell.
14. The vector according to claim 13 , wherein the DNA encodes a polypeptide selected from a group consisting of SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.
15. The vector according to claim 13 , comprising an isolated DNA according to claim 8 .
16. The vector according to claim 13 , comprising an isolated DNA according to claim 9 .
17. The vector according to claim 14 , wherein said DNA is ligated to DNA encoding the human growth hormone signal peptide.
18. A pharmaceutical composition comprising an isolated DNA molecule according to claim 1 and a pharmaceutically acceptable carrier.