Compositions and methods for modulating γ-c-cytokine activity
The γc-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. The present embodiments relate to the design of peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity. In several embodiments, peptide antagonists exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.
1. An isolated or purified peptide comprising amino acid sequence I-K-E-F-L-Q-R-F-I-H-I-V-Q-S-I-I-N-T-S (SEQ ID NO: 1), wherein the peptide inhibits the activity of one or more γc-cytokines selected from the group consisting of: IL-2, IL-4, IL-7, IL-9, IL-15 or IL-21.
2. The isolated or purified peptide of claim 1 , wherein the isolated or purified peptide further comprises a conjugate at the N-termini, C-termini or side residues of the peptide.
3. The isolated or purified peptide of claim 2 , wherein the conjugate is selected from the group consisting of: bovine serum albumin (BSA), albumin, Keyhold Limpet Hemocyanin (KLH), Fc region of IgG, a biological protein that functions as scaffold, an antibody against a cell-specific antigen, a receptor, a ligand a metal ion and Poly Ethylene Glycol (PEG).
4. The isolated or purified peptide of claim 1 , wherein the isolated or purified peptide further comprises a signal peptide.
5. The isolated or purified peptide of claim 1 , wherein the isolated or purified peptide further comprises a peptide that stabilizes the structure of the peptide and improves its biological activity.
6. The isolated or purified peptide of claim 1 , wherein the isolated or purified peptide further comprises one or more pharmaceutically acceptable diluents, emulsifying compounds, solubilizers, adjuvants, and carriers.
7. The isolated or purified peptide of claim 1 , wherein the isolated or purified peptide consists essentially of amino acid sequence I-K-E-F-L-Q-R-F-I-H-I-V-Q-S-I-I-N-T-S (SEQ ID NO: 1).