Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA, 93106, USA.
Center for Bioengineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA.
Angew Chem Int Ed Engl. 2020 Oct 12;59(42):18442-18445. doi: 10.1002/anie.202007256. Epub 2020 Aug 17.
The ability to monitor drug and biomarker concentrations in the body with high frequency and in real time would revolutionize our understanding of biology and our capacity to personalize medicine. The few in vivo molecular sensors that currently exist, however, all rely on the specific chemical or enzymatic reactivity of their targets and thus are not generalizable. In response, we demonstrate here an electrochemical sensing architecture based on binding-induced protein folding that is 1) independent of the reactivity of its targets, 2) reagentless, real-time, and with a resolution of seconds, and 3) selective enough to deploy in undiluted bodily fluids. As a proof of principle, we use the SH3 domain from human Fyn kinase to build a sensor that discriminates between the protein's peptide targets and responds rapidly and quantitatively even when challenged in whole blood. The resulting sensor architecture could drastically expand the chemical space accessible to continuous, real-time biosensors.
通过高频实时监测体内药物和生物标志物浓度，将彻底改变我们对生物学的理解以及实现个体化医疗的能力。然而，目前为数不多的体内分子传感器都依赖于其目标的特定化学或酶反应性，因此不具有通用性。有鉴于此，我们在这里展示了一种基于结合诱导蛋白折叠的电化学传感架构，该架构 1）不依赖于其目标的反应性，2）无需试剂，实时且具有秒级分辨率，3）具有足够的选择性，可用于未稀释的体液。作为原理验证，我们使用来自人类 Fyn 激酶的 SH3 结构域构建了一个传感器，该传感器可区分蛋白质的肽靶标，即使在全血中受到挑战，也能快速且定量地做出响应。由此产生的传感器架构可以极大地扩展可用于连续实时生物传感器的化学空间。
