Anti-angiogenic peptides from the n-terminus of endostatin

Abstract

Provided herein are anti-angiogenic comprising the N-terminal end of endostatin, nucleic acids encoding the same, pharmaceutical preparations comprising an effective amount of the peptide and nucleic acids and use of the pharmaceuticals in treating or preventing diseases or conditions associated with undesirable angiogenesis.

1 . An isolated peptide comprising about 10 to about 35 amino acids of the N-terminal region of an endostatin protein including the first histidine of the endostatin protein, or a variant thereof, wherein the isolated peptide or variant thereof has anti-tumor activity. 
     
     
         2 . The isolated peptide of  claim 1 , comprising from about 20 to about 30 amino acids. 
     
     
         3 . The isolated peptide of  claim 1 , which is selected from the group consisting of SEQ ID NOs: 2, 4, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 125, 126, 128, 129, 130, and 131. 
     
     
         4 . The isolated peptide of  claim 1 , comprising SEQ ID NO: 2. 
     
     
         5 . The isolated peptide of  claim 1 , comprising SEQ ID NO: 4. 
     
     
         6 . The isolated peptide of  claim 1 , comprising about 12 amino acids of SEQ ID NOs: 2 or 4. 
     
     
         7 . A nucleic acid encoding an isolated peptide or variant thereof of  claim 1 . 
     
     
         8 . A nucleic acid which is selected from the group consisting of SEQ ID NOs: 1, 3, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, and 123. 
     
     
         9 . A vector comprising a nucleic acid of  claim 7 . 
     
     
         10 . A pharmaceutical composition comprising an isolated peptide or variant thereof of  claim 1 . 
     
     
         11 . A pharmaceutical composition of  claim 10 , further comprising a second peptide. 
     
     
         12 . A pharmaceutical composition of  claim 10 , further comprising an effective amount of zinc. 
     
     
         13 . A device for introducing a composition into a subject comprising the pharmaceutical composition of  claim 10 . 
     
     
         14 . The device of  claim 13  that is a stent or a syringe. 
     
     
         15 . A method of preventing angiogenesis in a tissue, comprising contacting a tissue with a peptide of  claim 1  to thereby prevent angiogenesis. 
     
     
         16 . A method of preventing tumor growth in a tissue, comprising contacting the tissue with a peptide of  claim 1  to thereby prevent tumor growth. 
     
     
         17 . A method for preventing angiogenesis in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a peptide of  claim 1 , to thereby prevent angiogenesis in the subject. 
     
     
         18 . A method for preventing tumor growth in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a peptide of  claim 1 , to thereby prevent tumor growth in the subject. 
     
     
         19 . A method for treating or preventing an angiogenic associated disease in a subject comprising administering to the subject a pharmaceutical composition of  claim 11 . 
     
     
         20 . The method of  claim 21 , wherein the angiogenic associated disease is selected from the group consisting of: atherosclerosis, hemangioma, cancer, solid tumors, leukemia, metastasis, telangiectasia psoriasis scleroderma, pyogenic granuloma, myocardial angiogenesis, plaque neovascularization, coronary collaterals, cerebral collaterals, arteriovenous malformations, ischemic limb angiogenesis, corneal diseases, rubeosis, neovascular glaucoma, diabetic retinopathy, retrolental fibroplasia, arthritis, diabetic neovascularization, macular degeneration, wound healing, peptic ulcer, fractures, keloids, phemphigoid, trachoma, vasculogenesis and hematopoiesis. 
     
     
         21 . A method of treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a peptide of  claim 1 , to thereby treat cancer in the subject. 
     
     
         22 . The method of  claim 1 , wherein the cancer is selected from the group consisting of: endometrial, breast, prostate, colon, lung, liver, lymph node, kidney, pancreas, prostate, ovary, spleen, small intestine, stomach, skin, testes, head and neck, esophagus, brain (glioblastomas, medulloblastoma, astrocytoma, oligodendroglioma, ependymomas), blood cells, and bone marrow.