Peptides having anti-inflammatory properties
Aspects of the present invention relate to peptides having anti-inflammatory activity, compositions containing one or more of the peptides, and use of the peptides to treat conditions associated with excessive inflammation in animals, particularly humans and other mammals.
1. An anti-inflammatory composition comprising a peptide, wherein the peptide comprises one of the amino acid sequences selected from the group consisting of: SEQ ID NO: 121, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 120.
2. The anti-inflammatory composition of claim 1 , wherein the peptide binds to the dimerization site on a NFkB Class II protein.
3. The anti-inflammatory composition of claim 1 , wherein the peptide binds to human serum albumin.
4. The anti-inflammatory composition of claim 1 , wherein the peptide consists essentially of one of the amino acid sequences selected from the group consisting of: SEQ ID NO: 121, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 120.
5. The anti-inflammatory composition of claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:121.
6. The anti-inflammatory composition of claim 1 , wherein the peptide consists essentially of the amino acid sequence of SEQ ID NO:121.
7. The anti-inflammatory composition of claim 2 , wherein the peptide binds to the dimerization site on Rel B (SEQ ID NO: 367) and wherein:
(i) the peptide binds with a binding energy of at least −650 kcal/mol;
(ii) the peptide directly contacts at least one amino acid residue of Rel B selected from the group consisting of Glu 298, Tyr-300, Leu-301, Leu-302, Asp-330, His-332, and Leu-371; or
(iii) the peptide, when bound to the dimerization site on Rel B, forms an ionic bond with Asp-330, forms an ionic bond with His-332, and/or makes a hydrophobic contact with Leu-371.
8. The anti-inflammatory composition of claim 1 , wherein the peptide binds to CD206 (SEQ ID NO: 379) and wherein:
(i) the peptide binds to the mannose-binding site on CD206 and/or interferes with or blocks the binding of SIRP-mannose to CD206;
(ii) the peptide binds with a binding energy of at least −650 kcal/mol; or
(iii) the peptide directly contacts at least one amino acid residue of CD206 selected from the group consisting of Phe-708, Thr-709, Trp-710, Pro-714. Glu-719, Asn-720, Trp-721, Ala-722, Glu-725, Tyr-729, Glu-733, Asn-747, Asp-748, Ser-1691, Cys-1693, Phe-1694, and Phe-1703.
9. The anti-inflammatory composition of claim 1 , wherein the peptide binds to at least one signaling molecule selected from the group consisting of TGFβ (SEQ ID NO: 368), Notch1 (SEQ ID NO: 369), Wnt8R (SEQ ID NO: 370), TRAIL (SEQ ID NO: 371), IL6R (SEQ ID NO: 372), IL10R (SEQ ID NO: 373), EGFR (SEQ ID NO: 374), CDK6 (SEQ ID NO: 375), Histone Methyl Transferase (HMT) (SEQ ID NO: 376), CD47 (SEQ ID NO: 377), SIRP-α (SEQ ID NO: 378), CD206 (SEQ ID NO: 379), TGM2 (SEQ ID NO: 380); LEGUMAIN (SEQ ID NO: 413), CD209 (SEQ ID NO: 414), FAS (SEQ ID NO: 415), PD-1 (SEQ ID NO: 416), MKK7 (SEQ ID NO: 417), and RNR (SEQ ID NO: 418).
10. The anti-inflammatory composition of claim 1 , wherein the composition further comprises a second peptide, wherein the second peptide comprises one of the amino acid sequences selected from the group consisting of: SEQ ID NO: 121, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 120, wherein the first and second peptides can have the same or different sequences.
11. The anti-inflammatory composition of claim 10 , wherein the first and second peptides are linked together by a peptide bond, a peptide linker, or a non-peptide linker.
12. The anti-inflammatory composition of claim 1 , wherein the composition is free of protein other than the peptide.
13. A pharmaceutical composition comprising the anti-inflammatory composition of claim 1 and a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , wherein the composition further comprises a chemotherapeutic agent.
15. The pharmaceutical composition of claim 13 , wherein the composition further comprises a Chimeric Antigen Receptor/T Cell therapy.
16. The pharmaceutical composition of claim 14 , wherein the chemotherapeutic agent is selected from the group consisting of Gemcitabine, Docetaxel, Bleomycin, Erlotinib, Gefitinib, Lapatinib, Imatinib, Dasatinib, Nilotinib, Bosutinib, Crizotinib, Ceritinib, Trametinib, Bevacizumab, Sunitinib, Sorafenib, Trastuzumab, Ado-trastuzumab emtansine, Rituximab, Ipilimumab, Rapamycin, Temsirolimus, Everolimus, Methotrexate, Doxorubicin, Abraxane, Folfirinox, Cisplatin, Carboplatin, 5-fluorouracil, Teysumo, Paclitaxel, Prednisone, Levothyroxine, and Pemetrexed.
17. A method of treating a condition associated with chronic inflammation, the method comprising administering a pharmaceutical composition according to claim 13 to a subject suffering from the condition.
18. The method of claim 17 , wherein the condition is selected from the group consisting of: irritable bowel disease, ulcerative colitis, colitis, Crohn's disease, idiopathic pulmonary fibrosis, asthma, keratitis, arthritis, osteoarthritis, rheumatoid arthritis, auto-immune diseases, a feline or human immunodeficiency virus (FIV or HIV) infection, cancer, pulmonary fibrosis, dermal fibrosis, hepatic fibrosis, renal fibrosis, and fibrosis caused by ionized radiation.
19. The method of claim 17 , wherein the subject is a mammal.
20. The method of claim 19 , wherein the subject is a human.
21. The method of claim 17 , wherein the method reduces the level of at least one pro-inflammatory cytokine selected from group consisting of TNFα, IL1, IL6, IL12, MMP-1, MMP-9, MCP-1, IL8, IL17, and IL23.
22. The method of claim 21 , wherein the level of the at least one cytokine is reduced by at least 10%.
23. The pharmaceutical composition of claim 13 , wherein the anti-inflammatory composition comprises a peptide comprising the amino acid sequence of SEQ ID NO:121.
24. The pharmaceutical composition of claim 13 , wherein the anti-inflammatory composition comprises a peptide consisting essentially of the amino acid sequence of SEQ ID NO:121.
25. The method of claim 17 , wherein the wherein the anti-inflammatory composition comprises a peptide comprising the amino acid sequence of SEQ ID NO:121.
26. The method of claim 17 , wherein the anti-inflammatory composition comprises a peptide consisting essentially of the amino acid sequence of SEQ ID NO:121.