Immunomodulatory peptides

1. A peptide having the sequence:

wherein:

at least one of A, B, and Y is present and comprises a hydrophilic polymer; and wherein

A, if present, comprises a hydrophilic polymer or is hydrogen, acyl, or an amino protecting group;

B, if present, comprises a hydrophilic polymer or is an amino group, a hydroxyl group, or a carboxy protecting group;

X 0 , if present, is an optionally derivatized amino acid or an analog thereof or an optionally derivatized peptide of 2-15 amino acids or an analog thereof;

X 1 , if present, is an optionally derivatized amino acid or an analog thereof;

X 2 , if present, is an amino acid or an analog thereof;

X 3 is an amino acid or analog thereof that is capable of forming a bridge with X 10 , X 12 or X 13 ,

X 4 is an optionally derivatized amino acid or an analog thereof or an optionally derivatized peptide of 2 or 4 amino acids or an analog thereof;

X 6 is a basic amino acid or an analog thereof, an aromatic amino acid or an analog thereof, or a basic aromatic amino acid or an analog thereof;

X 7 is phenylalanine or an analog thereof;

X 8 and X 9 are each independently chosen from glycine or an analog thereof, sarcosine or an analog thereof, aspartic acid or an analog thereof, a D -amino acid or an analog thereof, and α-aminoisobutyric acid or an analog thereof, or

X 8 , when taken together with X 9 , forms a dipeptide analog;

X 10 is an amino acid or an analog thereof, or

X 10 , when taken together with X 9 , forms a dipeptide analog;

X 11 is tyrosine or an analog thereof;

X 12 is an optionally derivatized amino acid or an analog thereof;

X 13 , if present, is an amino acid or an analog thereof;

X 14 , if present, is an optionally derivatized amino acid or an analog thereof or an optionally derivatized peptide of 2-15 amino acids or an analog thereof;

Y comprises a hydrophilic polymer;

Z is a linker that attaches to each peptide monomer through

A;

B;

the amino terminus or a side chain of X 0 , if X 0 is present; to the amino terminus or side chain of X 1 , if X 0 is absent; to the amino terminus or side chain of X 2 , if both X 0 and X 1 are absent; or to the amino terminus or side chain of X 3 , if X 0 , X 1 and X 2 are absent; or

the carboxy terminus or a side chain of X 14 , if X 14 is present; to the carboxy terminus or a side chain of X 13 , if X 14 is absent; or to the carboxy terminus or a side chain of X 12 if both X 13 and X 14 are absent;

m is an integer chosen from 1, 2, and 3; and

n is an integer chosen from 1, 2, and 3;

wherein:

each A, B, X 0 , X 1 , X 2 , X 3 , X 4 , X 6 , X 7 , X 8 , X 9 , X1 0 , X 11 , X 12 , X 13 , and X 14 is chosen independently; and

each monomer of the peptide ranges from 10 to 50 amino acids in length.

2. The peptide of claim 1 having the sequence:

wherein:

X 1 is an underivatized amino acid or an underivatized amino acid analog;

X 4 is an underivatized peptide of 1, 2, or 4 amino acids or analogs thereof; and

X 12 is an underivatized amino acid or an underivatized amino acid analog.

3. The peptide of claim 1 , wherein the peptide is unbridged.

4. The peptide of claim 1 , wherein X 3 forms a bridge with X 13 .

5. The peptide of claim 4 , wherein the bridge is a side chain to side chain bridge.

6. The peptide of claim 1 , wherein X 6 is histidine or an analog thereof.

7. The peptide of claim 1 , wherein at least one of X 8 and X 9 is chosen from glycine, D -amino acids, α-aminoisobutyric acid, and sarcosine.

8. The peptide of claim 1 , wherein the peptide has the sequence:

9. The peptide of claim 8 , wherein the peptide has the sequence:

wherein horizontal brackets indicate the presence of a bridge.

10. The peptide of claim 1 , wherein the hydrophilic polymer is chosen from polyethylene glycol, polypropylene glycol, dextran; cellulose, methylcellulose, hydroxycellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethyl cellulose, hydroxyalkyl starch, polyvinyl alcohol, poly(N-vinyl pyrrolidone), poloxamers, and polyethylene glycol copolymers.

11. The peptide of claim 10 , wherein the hydrophilic polymer is polyethylene glycol (PEG).

12. The peptide of claim 11 , wherein the PEG is a linear PEG.

13. The peptide of claim 11 , wherein the PEG is a branched PEG.

14. The peptide of claim 11 , wherein the PEG has an average molecular weight ranging from 10-60 kDa.

15. The peptide of claim 1 , wherein the peptide binds specifically to human FcRn.

16. The peptide of claim 15 , wherein the affinity of the peptide for human FcRn ranges from 50 fM to 1 mM.

17. The peptide of claim 15 , wherein the peptide inhibits the binding of human FcRn to human IgG, and has an IC 50 ranging from 50 fM to 1 mM.

18. The peptide of claim 1 , wherein the peptide has the sequence:

19. The peptide of claim 18 , wherein the peptide has the sequence:

wherein horizontal brackets indicate the presence of a bridge.

20. The peptide of claim 19 , wherein the peptide has the sequence: