Phenylalanine Monitoring via Aptamer-Field-Effect Transistor Sensors
Phenylalanine Monitoring via Aptamer-Field-Effect Transistor Sensors
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DOI：
10.1021/acssensors.9b01963
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发表时间：
2019-12-01
期刊：
影响因子：
8.9
通讯作者：
Andrews, Anne M.
中科院分区：
文献类型：
--
作者：
Cheung, Kevin M.;Yang, Kyung-Ae;Andrews, Anne M.
苯丙氨酸的测定对于苯丙酮尿症患者的终身疾病管理非常重要，苯丙酮尿症是一种遗传性疾病，其中苯丙氨酸积累并持续存在于改变大脑发育并导致永久性神经损伤和认知功能障碍的水平。最近治疗苯丙酮尿症的方法集中在注射药物，有效地分解苯丙氨酸，但有时会导致精神上低苯丙氨酸水平。我们已经确定了两种形式的苯丙氨酸新的DNA适体，最初作为荧光传感器，然后，与场效应晶体管（FET）。适体-FET传感器在宽范围的浓度（fM至mM）内检测苯丙氨酸。对氯苯丙氨酸抑制将苯丙氨酸转化为酪氨酸的酶，用于在小鼠脑发育期间诱导高苯丙氨酸血症。适体-FET传感器对苯丙氨酸与对氯苯丙氨酸特异，并在患者预期水平下区分小鼠血清苯丙氨酸的变化。适体-FET可用于在存在结构相关酶抑制剂以及天然存在的氨基酸的情况下研究高苯丙氨酸血症模型。基于核酸的受体，区分苯丙氨酸类似物，一些不同的是一个单一的取代基，表明一个完善的能力，以确定适配体与结合口袋定制的高亲和力和特异性。整合到FET中的这种类型的适体能够实现快速、电子、无标记的苯丙氨酸感测。
Determination of the amino acid phenylalanine is important for lifelong disease management in patients with phenylketonuria, a genetic disorder in which phenylalanine accumulates and persists at levels that alter brain development and cause permanent neurological damage and cognitive dysfunction. Recent approaches for treating phenylketonuria focus on injectable medications that efficiently break down phenylalanine but sometimes result in detrimentally low phenylalanine levels. We have identified new DNA aptamers for phenylalanine in two formats, initially as fluorescent sensors and then, incorporated with field-effect transistors (FETs). Aptamer-FET sensors detected phenylalanine over a wide range of concentrations (fM to mM). para-Chlorophenylalanine, which inhibits the enzyme that converts phenylalanine to tyrosine, was used to induce hyperphenylalaninemia during brain development in mice. Aptamer-FET sensors were specific for phenylalanine versus para-chlorophenylalanine and differentiated changes in mouse serum phenylalanine at levels expected in patients. Aptamer-FETs can be used to investigate models of hyperphenylalanemia in the presence of structurally related enzyme inhibitors, as well as naturally occurring amino acids. Nucleic acid-based receptors that discriminate phenylalanine analogs, some that differ by a single substituent, indicate a refined ability to identify aptamers with binding pockets tailored for high affinity and specificity. Aptamers of this type integrated into FETs enable rapid, electronic, label-free phenylalanine sensing.