Peptide conjugates
Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.
1. A therapeutic composite peptide conjugate, wherein the therapeutic composite peptide conjugate inhibits an activity of at least two cytokines selected from a family of cytokines that bind to a common receptor, wherein the therapeutic composite peptide conjugate comprises a therapeutic composite peptide conjugated to a moiety;
wherein the therapeutic peptide conjugate is 11-50 amino acids in length;
wherein the therapeutic peptide comprises a region 1-20 amino acids in length that aligns with a corresponding region of a single target ligand or receptor; and
wherein the single target ligand or receptor is of any one of SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, and SEQ ID NO:161.
2. The therapeutic composite peptide conjugate of claim 1 , wherein the moiety is a selected from the group consisting of a biological protein, BSA, albumin, immunoglobulin, antibody fragment, Fc region of IgG, a scaffold protein, carbohydrate, and polyethylene glycol.
3. The therapeutic composite peptide conjugate of claim 2 , wherein the therapeutic composite peptide is conjugated to an N-terminus, C-terminus and/or a side residue of the moiety.
4. The therapeutic composite peptide conjugate of claim 1 , wherein the moiety enables efficient delivery and improved biological stability therapeutic composite peptide conjugate in vivo.
5. The therapeutic composite peptide conjugate of claim 1 , wherein the family of cytokines is selected from the group consisting of γc-family of cytokines, IL-6 family of cytokines, and IL-17 family of cytokines.
6. The therapeutic composite peptide conjugate of claim 5 , wherein the γc-family of cytokines consists of IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, the IL-6 family of cytokines consists of IL-6, IL-11, CNTF, CT-1, OSM, LIF, and IL-27, and the IL-17 family of cytokines consists of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E (IL-25), and IL-17F.
7. The therapeutic composite peptide conjugate of claim 1 , wherein the therapeutic composite peptide conjugate is used to ameliorate and/or treat a disease selected from the group consisting of a γc-cytokine-mediated disease, an HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) associated disease, and an inflammatory respiratory disease.
8. The therapeutic composite peptide conjugate of claim 7 , wherein the γc-cytokine-mediated disease is selected from the group consisting of CD4-leukemia, CD8-leukemia, LGL-leukemia, systemic lupus erythematosus, Sjögren's syndrome, Wegener's granulomatosis, Celiac disease, Hashimoto's thyroiditis, rheumatoid arthritis, inflammatory bowel disease, diabetes mellitus, psoriasis, multiple sclerosis, uveitis, inflammation of the eye, and graft-versus-host disease (GvHD).
9. The therapeutic composite peptide conjugate of claim 7 , wherein the HAM/TSP associated disease is selected from the group consisting of Adult T-cell Leukemia (ATL), HTLV-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), and other non-neoplastic inflammatory diseases associated with HTLV.
10. The therapeutic composite peptide conjugate of claim 7 , wherein the inflammatory respiratory disease is selected from the group consisting of asthma, sinusitis, hay fever, bronchitis, chronic obstructive pulmonary disease (COPD), allergic rhinitis, acute and chronic otitis, and lung fibrosis.
11. The therapeutic composite peptide conjugate of claim 1 , wherein the therapeutic composite peptide conjugate is used for a cosmetic purpose.
12. The therapeutic composite peptide conjugate of claim 11 , wherein the cosmetic purpose is selected from the group consisting of treatment of acne, treatment of hair loss, treatment of sunburn, nail maintenance, and reduction in the appearance of aging.