Salt-Mediated Nanopore Detection of ADAM-17
Salt-Mediated Nanopore Detection of ADAM-17
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DOI：
10.1021/acsabm.8b00689
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发表时间：
2019-01-22
影响因子：
4.7
通讯作者：
Guan, Xiyun
中科院分区：
文献类型：
--
作者：
Chen, Xiaohan;Zhang, Youwen;Guan, Xiyun
ADAM-17（一种解整合素和金属蛋白酶 17）在各种生理和病理生理过程中发挥着重要作用。 ADAM-17 的过度表达/表达不足可能导致多种疾病。在这项工作中，通过利用离子强度和盐梯度，并监测纳米孔中底物肽和 ADAM-17 之间的酶裂解反应，我们开发了一种用于快速检测 ADAM-17 的无标记传感器。该传感器具有高度灵敏性和选择性：皮摩尔浓度的 ADAM-17 可以在几分钟内检测到，而结构相似的蛋白酶（例如 ADAM-9 和 MMP-9）不会干扰其检测。鉴于MMP/ADAM作为人类癌症早期检测和治疗的有价值的生物标志物和潜在治疗靶点的重要性，本工作中开发的基于纳米孔的蛋白酶检测策略可能会在疾病诊断和药物筛选中找到潜在的应用。
ADAM-17 (a disintegrin and metalloproteinase 17) plays an important role in various physiological and pathophysiological processes. Overexpression/underexpression of ADAM-17 could lead to various diseases. In this work, by taking advantage of ionic strength and salt gradient, and monitoring the enzymatic cleavage reaction between a substrate peptide and ADAM-17 in a nanopore, we developed a label-free sensor for the rapid detection of ADAM-17. The sensor was highly sensitive and selective: picomolar concentrations of ADAM-17 could be detected within minutes, whereas structurally similar proteases such as ADAM-9 and MMP-9 did not interfere with its detection. Given the importance of MMPs/ADAMs as valuable biomarkers and potential therapeutic targets for the early detection and treatment of human cancers, the nanopore-based protease detection strategy developed in this work may find potential applications in disease diagnosis and drug screening.