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    Detection of Disease Associated Proteolysis
    3.
    发明申请
    Detection of Disease Associated Proteolysis 审中-公开
    疾病相关蛋白水解检测

    公开(公告)号：US20090035797A1

    公开(公告)日：2009-02-05

    申请号：US11665403

    申请日：2005-10-17

    申请人： William S. Hancock ,  Haven Baker ,  Marina Hincapie ,  Xiaoyang Zheng

    发明人： William S. Hancock ,  Haven Baker ,  Marina Hincapie ,  Xiaoyang Zheng

    IPC分类号： C12Q1/37 ,  C12Q1/02 ,  C07K1/20 ,  G01N33/48 ,  C12Q1/00

    CPC分类号： G01N33/6848

    摘要： Described herein are methods and techniques to study the “degradome”. The degradome of a specific protease is the complete product of the natural substrate repertoire of that enzyme in a cell, tissue or organism. The complete set of proteases that are expressed at a particular moment or circumstance by a cell, tissue or organism produces the collective degradome. Included in the methods described herein are approaches that allow the direct identification and characterization of degradome peptides from approx. 400 to approx. 12,000 Da. The methods of the invention avoid the inherent problems of studying the peptidome by focusing on specific or unique proteolytic cleavages that occur as a result of endogenous protease activity induced by specific diseases. Once characterized, the presence of, or change in level of, specific peptides of the degradome can be used, e.g., to identify specific peptides having elevated levels compared to a reference normal/or to correlate identified peptides with specific proteins and/or to identify protein fragmentation patterns (e.g., peptide ladders) and the specific protease(s) that brought them about and then correlate this information with the presence or absense of a specific disease or condition. Thus, the methods of the invention can be used, for example, to identify new diagnostic markers and/or therapeutic targets, as specific clinical diagnostic methods for individual patients and as methods of monitoring the progress of a therapeutic regimen for the treatment of a patient.

    摘要翻译： 本文描述了研究“降解物”的方法和技术。 特定蛋白酶的降解物是细胞，组织或生物体中该酶的天然底物的全部产物。 在细胞，组织或生物体的特定时刻或环境下表达的完整蛋白酶产生集体降解物。 包括在本文描述的方法中的方法是允许直接鉴定和表征降解物肽。 400到约 12,000 Da。 本发明的方法通过集中于由特定疾病诱导的内源性蛋白酶活性而产生的特异性或独特的蛋白水解裂解来避免研究肽酶的固有问题。 一旦表征，可以使用降解物的特异性肽的存在或水平的变化，例如，鉴定与参考标准相比具有升高的水平的特异性肽，或将鉴定的肽与特异性蛋白质相关联和/或鉴定 蛋白质断裂模式（例如，肽梯）和特异性蛋白酶，使其与特定疾病或病症的存在或缺失相关联。 因此，本发明的方法可用于例如鉴定新的诊断标记物和/或治疗靶标，作为个体患者的特定临床诊断方法，以及监测用于治疗患者的治疗方案进展的方法 。