Protease Substrate Array

描述(申请人提供)：这项提案寻求开发一种新的基于微珠的阵列技术，用于同时测量小体积细胞或生物液中的蛋白酶的催化活性。需要这种技术来加快基于蛋白质组学的诊断和药物发现的研究，方法是使分子表型能够跨越大量人群，并大规模、大规模地平行筛选调节蛋白酶活性的药物先导。将开发允许对珠上的种群进行多重蛋白酶分析的方法，其中每个珠类型的种群对特定的蛋白酶是特定的。这项技术的基础和诊断应用将使我们能够仔细检查心血管疾病、癌症、传染病和某些遗传性疾病的分子基础，以及筛选和鉴定可能干扰这些酶的致病异常的蛋白酶抑制剂。这种多重酶分析形式的优点是能够在同一筛选中筛选抑制物以及抑制的特异性。

DESCRIPTION (provided by applicant): This proposal seeks to develop a new bead-based array technology for simultaneously measuring catalytic activity of proteases in small volumes of cells or biological fluids. Technology of this kind is needed to accelerate research in proteomics-based diagnostics and drug discovery by enabling molecular phenotyping across large populations, and the large-scale, massively parallel screening for drug leads, which modulate protease activity. Methods will be developed that allow multiplexed protease assays to be carried out on populations on beads, with each bead-type of the population being specific to a particular protease. Basic and diagnostic applications of this technology will enable careful examination of the molecular basis of cardiovascular disease, cancer, infectious disease, and certain genetic disorders, as well as the screening for and identification of protease inhibitors, which may interfere with pathogenic aberrations of such proteases. An advantage of such multiplexed enzyme assay format is the ability to screen for inhibitors, as well as specificity of inhibition in the same screen.