De novo design of potent and selective interleukin mimetics
De novo designed polypeptides that bind to IL-2 receptor β c heterodimer (IL-2Rβ c ), IL-4 receptor α c heterodimer (IL-4Rα c ), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.
1. A non-naturally occurring polypeptide comprising an amino acid sequence at least 80% identical to the amino acid sequence set forth in SEQ ID NO:181 provided that a cysteine residue is at amino acid position 62, 69 or 73 of SEQ ID NO:181, wherein the polypeptide binds to IL-2 receptor β c heterodimer (IL-2Rβ c ).
2. The non-naturally occurring polypeptide of claim 1 comprising an amino acid sequence at least 90% identical to the amino acid sequence set forth in SEQ ID NO:181 provided that a cysteine residue is at amino acid position 62, 69 or 73 of SEQ ID NO:181.
3. The non-naturally occurring polypeptide of claim 2 comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO:181 provided that a cysteine residue is at amino acid position 62, 69 or 73 of SEQ ID NO:181.
4. The non-naturally occurring polypeptide of claim 1 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
5. The non-naturally occurring polypeptide of claim 4 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
6. The non-naturally occurring polypeptide of claim 2 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
7. The non-naturally occurring polypeptide of claim 6 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
8. The non-naturally occurring polypeptide of claim 3 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
9. The non-naturally occurring polypeptide of claim 8 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
10. The non-naturally occurring polypeptide of claim 1 wherein the cysteine residue is at amino acid position 62 of SEQ ID NO: 181.
11. The non-naturally occurring polypeptide of claim 2 wherein the cysteine residue is at amino acid position 62 of SEQ ID NO: 181.
12. The non-naturally occurring polypeptide of claim 3 wherein the cysteine residue is at amino acid position 62 of SEQ ID NO: 181.
13. The non-naturally occurring polypeptide of claim 3 comprising the amino acid sequence as set forth in SEQ ID NO: 195.
14. The non-naturally occurring polypeptide of claim 10 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
15. The non-naturally occurring polypeptide of claim 14 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
16. The non-naturally occurring polypeptide of claim 11 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
17. The non-naturally occurring polypeptide of claim 16 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
18. The non-naturally occurring polypeptide of claim 12 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
19. The non-naturally occurring polypeptide of claim 18 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
20. The non-naturally occurring polypeptide of claim 13 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
21. The non-naturally occurring polypeptide of claim 20 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
22. The non-naturally occurring polypeptide of claim 1 wherein the cysteine residue is at amino acid position 69 of SEQ ID NO: 181.
23. The non-naturally occurring polypeptide of claim 3 wherein the cysteine residue is at amino acid position 69 of SEQ ID NO: 181.
24. The non-naturally occurring polypeptide of claim 22 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
25. The non-naturally occurring polypeptide of claim 24 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
26. The non-naturally occurring polypeptide of claim 1 wherein the cysteine residue is at amino acid position 73 of SEQ ID NO: 181.
27. The non-naturally occurring polypeptide of claim 3 wherein the cysteine residue is at amino acid position 73 of SEQ ID NO: 181.
28. The non-naturally occurring polypeptide of claim 26 further comprising a polyethylene glycol containing moiety linked to the cysteine residue.
29. The non-naturally occurring polypeptide of claim 28 wherein the polyethylene glycol is linked via a maleimide group to the cysteine residue.
30. A pharmaceutical composition comprising the polypeptide of claim 1 , and a pharmaceutically acceptable carrier.