Use of peptides as therapeutic agent for autoimmune diseases and bone diseases

Abstract

The present invention relates to use of peptides as a therapeutic agent, wherein it has been confirmed that the peptides of the present invention significantly inhibit the activity of T cells and the differentiation of T helper 17 cells (Th17 cells), which are associated with autoimmune disease, and have remarkable effects of treating and improving arthritis in an animal model of arthritis. Therefore, the peptides may be used as an active ingredient in therapeutic agents for various autoimmune diseases such as bone disease, inflammatory disease or rheumatoid arthritis.

1 . A synthetic peptide consisting of an amino acid sequence of Formula 1 below:
   (X 1 -X 2 -X 3 ) n   [Formula 1]
   wherein, X 1  to X 3  each is as below:   i) X 1  is proline (P), each of X 2  and X 3  is serine (S);   ii) X 1  is proline (P), X 2  is threonine (T), X 3  is serine (S);   iii) each of X 1  and X 3  is serine (S), X 2  is proline (P),   n is an integer from 2 to 10, and   when n is 2, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 96,   when n is 3, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 97,   when n is 4, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 98,   when n is 5, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 99,   when n is 6, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 100,   when n is 7, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 101,   when n is 8, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 102,   when n is 9, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 103,   when n is 10, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 104.   
     
     
         2 . The synthetic peptide according to  claim 1 , wherein an N- or C terminus of the peptide is bound to a protective group selected from the group consisting of an acetyl group, a fluorenylmethoxy carbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, and polyethylene glycol (PEG). 
     
     
         3 . A method for treating bone disease, inflammatory disease or autoimmune disease, comprising administering a synthetic peptide consisting of an amino acid sequence of Formula 1 below in a pharmaceutically effective dose to a subject with bone disease, inflammatory disease or autoimmune disease:
   (X 1 -X 2 -X 3 ) n   [Formula 1]
   wherein, X 1  to X 3  each is as below:   i) X 1  is proline (P), each of X 2  and X 3  is serine (S);   ii) X 1  is proline (P), X 2  is threonine (T), X 3  is serine (S);   iii) each of X 1  and X 3  is serine (S), X 2  is proline (P),   n is an integer from 2 to 10, and   when n is 2, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 96,   when n is 3, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 97,   when n is 4, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 98,   when n is 5, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 99,   when n is 6, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 100,   when n is 7, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 101,   when n is 8, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 102,   when n is 9, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 103,   when n is 10, the amino acid sequence of Formula 1 is represented by SEQ ID NO: 104.   
     
     
         4 . The method according to  claim 3 , wherein the bone disease is at least one selected from the group consisting of arthritis, osteoporosis, bone metastatic cancer, solid cancer bone metastasis, musculoskeletal complications due to solid cancer bone metastasis, hypercalcemia caused by malignant tumor, multiple myeloma, primary bone tumor, periodontal disease, inflammatory alveolar bone disease, inflammatory bone resorption disease, and Paget's disease. 
     
     
         5 . The method according to  claim 3 , wherein the inflammatory disease is selected from the group consisting of atopy, psoriasis, dermatitis, allergies, arthritis, rhinitis, otitis media, sore throat, tonsillitis, cystitis, nephritis, pelvic inflammatory, Crohn's disease, ulcerative colitis, ankylosing spondylitis, systemic lupus erythematodes (SLE), asthma, edema, delayed allergy (Type IV allergy), transplant rejection, graft-versus-host disease, autoimmune encephalomyelitis, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, diabetic retinopathy, ischemic-reperfusion injury, vascular restenosis, glomerulonephritis, and gastrointestinal allergy. 
     
     
         6 . The method according to  claim 3 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, Sjogren's syndrome, systemic sclerosis, polymyositis, systemic angitis, mixed connective tissue disease, Crohn's disease, Hashimoto's disease, Grave's disease, Goodpasture's syndrome, Guillain-Barre syndrome, idiopathic thrombocytopenic purpura, irritable bowel syndrome, myasthenia gravis, narcolepsy, vulgaris ulcer, pernicious anemia, primary biliary cirrhosis, ulcerative colitis, vasculitis, Wegener's granulomatosis, and psoriasis.