Short peptides useful for treatment of ischemia/reperfusion injury and other tissue damage conditions associated with nitric oxide and its reactive species
    1.
    发明授权
    Short peptides useful for treatment of ischemia/reperfusion injury and other tissue damage conditions associated with nitric oxide and its reactive species 有权
    用于治疗与一氧化氮及其反应性物质相关的缺血/再灌注损伤和其他组织损伤病症的短肽

    公开(公告)号:US08389482B2

    公开(公告)日:2013-03-05

    申请号:US11744104

    申请日:2007-05-03

    IPC分类号: A61K38/07 A61K38/03

    摘要: This invention discloses isolated short peptides comprising the amino acid sequence Cys-Glu-Phe-His (CEFH; SEQ ID NOS: 1 and 15) and analogs thereof as well as compositions comprising CEFH peptides and analogs thereof. The CEFH peptides disclosed herein are effective in mediating the denitration of 3-nitrotyrosines (3-NT) in cellular proteins thereby preventing tissue damage associated with excess nitric oxide (NO) and its reactive species. The CEFH peptides disclosed herein are useful in the treatment of ischemia/reperfusion (I/R) injury of various tissues (e.g., I/R injury of heart muscle associated with heart attack or cardiac surgery, I/R injury of brain tissue associated with stroke, I/R injury of liver tissue, skeletal muscles, etc.), septic shock, anaphylactic shock, neurodegenerative diseases (e.g., Alzheimer's and Parkinson's diseases), neuronal injury, atherosclerosis, diabetes, multiple sclerosis, autoimmune uveitis, pulmonary fibrosis, oobliterative bronchiolitis, bronchopulmonary dysplasia (BPD), amyotrophic lateral sclerosis (ALS), sepsis, inflammatory bowel disease, arthritis, allograft rejection, autoimmune myocarditis, myocardial inflammation, pulmonary granulomatous inflammation, influenza- or HSV-induced pneumonia, chronic cerebral vasospasm, allergic encephalomyelitis, central nervous system (CNS) inflammation, Heliobacterium pylori gastritis, necrotizing entrerocolitis, celliac disease, peritonitis, early prosthesis failure, inclusion body myositis, preeclamptic pregnancies, skin lesions with anaphylactoid purpura, nephrosclerosis, ileitis, leishmaniasis, cancer, and related disorders.

    摘要翻译: 本发明公开了包含氨基酸序列Cys-Glu-Phe-His(CEFH; SEQ ID NO:1和15)及其类似物的分离的短肽,以及包含CEFH肽及其类似物的组合物。 本文公开的CEFH肽有效介导细胞蛋白质中3-硝基酪氨酸(3-NT)的脱硝,从而防止与过量一氧化氮(NO)及其反应物种相关的组织损伤。 本文公开的CEFH肽可用于治疗各种组织的缺血/再灌注(I / R)损伤(例如,与心脏病发作或心脏手术相关的心肌的I / R损伤,与...相关的脑组织的I / R损伤 脓毒性休克,过敏性休克,神经变性疾病(如阿尔茨海默病和帕金森病),神经元损伤,动脉粥样硬化,糖尿病,多发性硬化,自身免疫性葡萄膜炎,肺纤维化, 弥漫性细支气管炎,支气管肺发育不良(BPD),肌萎缩性侧索硬化(ALS),败血症,炎症性肠病,关节炎,同种异体移植排斥反应,自身免疫性心肌炎,心肌炎症,肺肉芽肿性炎症,流感或HSV感染性肺炎,慢性脑血管痉挛,过敏 脑脊髓炎,中枢神经系统(CNS)炎症,幽门螺杆菌胃炎,坏死性肠内炎,腹膜炎,腹膜炎,e 严重假体失败,包涵体肌炎,先兆子痫妊娠,具有过敏性紫癜的皮肤病变,肾硬化,回肠炎,利什曼病,癌症和相关疾病。