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. Peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity are described. In several embodiments, peptide antagonists simultaneously inhibit the activity of multiple γc-cytokine family members.
1. A composition comprising a modulator of γ-c-cytokine activity comprising peptide conjugate comprising partial amino acid sequences of at least two interleukin (IL) protein γ-c-box D-helix regions, said partial amino acid sequences consisting of one to ten amino acids of each of the at least two IL protein γ-c-box D-helix regions.
2. The composition of claim 1 , wherein said at least two IL protein γ-c-box D0helix regions are from IL proteins selected from the group consisting of IL-15, IL-2, IL-21, IL-4, IL-9, and IL-7.
3. The composition of claim 1 , wherein said partial amino acid sequences consist of one to six amino acids of each of the at least two IL protein γ-c-box D-helix regions.
4. The composition of claim 1 , wherein said modulator modulates the activity of two or more of said at least two IL proteins.
5. The composition of claim 1 , wherein said peptide conjugate comprises SEQ ID NO: 1.
6. The composition of claim 1 , wherein said peptide conjugate consists of SEQ ID NO: 1.
7. The composition of claim 1 , wherein the peptide conjugate comprises one or more non-natural amino acid.
8. The composition of claim 1 , wherein said peptide comprises a derivative of the amino acid sequence of SEQ ID NO: 1, said derivative sharing at least 90% with the amino acid sequence of SEQ ID NO: 1.
9. The composition of claim 1 , wherein said peptide comprises a derivative of the amino acid sequence of SEQ ID NO: 1, said derivative sharing at least 95% with the amino acid sequence of SEQ ID NO: 1.
10. A method of producing the modulator of γ-c-cytokine activity of the composition according to claim 1 , the method comprising chemically synthesizing the peptide conjugate.
11. A method of producing the modulator of γ-c-cytokine activity of the composition according to claim 1 , the method comprising expressing a polynucleotide encoding the peptide conjugate.