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 nucleotide sequence encoding 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, and wherein the therapeutic composite peptide conjugate comprises a therapeutic composite peptide conjugated to a moiety;
wherein the therapeutic composite 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 nucleotide sequence of claim 1 , wherein the nucleotide sequence is selected from the group consisting of dsDNA, ssDNA, dsRNA, and ssRNA.
3. The nucleotide sequence of claim 1 , wherein the nucleotide sequence further comprises a sequence encoding a signal peptide.
4. The nucleotide sequence 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.
5. The nucleotide sequence of claim 4 , 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.
6. The nucleotide sequence of claim 1 , wherein the moiety is selected from the group consisting of a biological protein, BSA, albumin, immunoglobulin, antibody fragment, Fc region of IgG, and a scaffold protein.
7. The nucleotide sequence of claim 1 , wherein the therapeutic composite peptide is conjugated to an N-terminus, C-terminus, and/or side residue of the moiety.
8. The nucleotide sequence of claim 1 , wherein the moiety enables efficient delivery and improved biological stability of the therapeutic composite peptide conjugate in vivo.
9. The nucleotide sequence of claim 1 , wherein the nucleotide sequence further comprises a sequence encoding a linker polypeptide.
10. A pharmaceutical composition comprising:
a nucleotide sequence encoding a therapeutic composite peptide conjugate; and
a pharmaceutical acceptable carrier, diluent, excipient or combination thereof; 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, and wherein the therapeutic composite peptide conjugate comprises a therapeutic composite peptide conjugated to a moiety;
wherein the therapeutic composite 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.
11. The pharmaceutical composition of claim 10 , wherein the nucleotide sequence is selected from the group consisting of dsDNA, ssDNA, dsRNA, and ssRNA.
12. The pharmaceutical composition of claim 10 , 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.
13. The pharmaceutical composition of claim 12 , 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.
14. The pharmaceutical composition of claim 10 , wherein the moiety is selected from the group consisting of a biological protein, BSA, albumin, immunoglobulin, antibody fragment, Fc region of IgG, and a scaffold protein.
15. The pharmaceutical composition of claim 10 , wherein the nucleotide sequence further comprises a sequence encoding a signal peptide.
16. The pharmaceutical composition of claim 10 , wherein the therapeutic composite peptide is conjugated to an N-terminus, C-terminus, and/or side residue of the moiety.
17. The pharmaceutical composition of claim 10 , wherein the moiety enables efficient delivery and improved biological stability of the therapeutic composite peptide conjugate in vivo.
18. The pharmaceutical composition of claim 10 , wherein the nucleotide sequence further comprises a sequence encoding a linker polypeptide.