Protease Substrate Array

描述（由申请人提供）：本提案旨在开发一种新的基于珠状阵列的技术，用于同时测量小体积细胞或生物液体中蛋白酶的催化活性。需要这种技术来加速基于蛋白质组学的诊断和药物发现的研究，通过在大量人群中实现分子表型，以及大规模，大规模平行筛选调节蛋白酶活性的药物先导。将开发允许对微球上的群体进行多重蛋白酶测定的方法，每个群体的头部类型对特定的蛋白酶具有特异性。这项技术的基础和诊断应用将能够仔细检查心血管疾病、癌症、传染病和某些遗传疾病的分子基础，以及筛选和鉴定可能干扰这些蛋白酶致病性畸变的蛋白酶抑制剂。这种多重酶分析格式的优点是能够筛选抑制剂，以及在同一筛选抑制的特异性。

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.