1,4-Dihydropyridine-based FA1 site-specific fluorescent probes for the selective detection and quantification of HSA levels in biofluids,Analyst

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1,4-Dihydropyridine-based FA1 site-specific fluorescent probes for the selective detection and quantification of HSA levels in biofluids
Analyst ( IF 3.6 ) Pub Date : 2024-07-30 , DOI: 10.1039/d4an00881b
S Shurooque Kanneth ₁ , V C Saheer ₂ , Lakshmi Chakkumkumarath ₁

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Human serum albumin (HSA) is a multifunctional circulatory protein essential for many physiological processes including oncotic pressure maintenance, ligand/drug binding and transport, antioxidant activity, etc. Abnormal HSA levels in biological fluids have been reported in a variety of clinical disorders, making it a potential biomarker for early diagnosis. Low serum albumin levels have been linked to increased long- and short-term mortality rates in ICU patients. Therefore, quantifying HSA in biofluids such as serum and urine offers a convenient approach for the early identification of underlying clinical conditions and assessing the risk factors. Herein, we report a series of fluorescent 1,4-dihydropyridine (DHP) derivatives for the detection and quantification of HSA in biofluids. Their response towards HSA can be tuned by varying the substituents at the C-4 and the N-1 of the DHP ring. Depending on the nature of the substituents, they generated either a turn-on or ratiometric response with a LoD in low nanomolar or subnanomolar levels. A pair of enantiomers obtained by introducing a chiral center on the N-substituents highlighted the importance of stereochemistry in HSA-ligand interactions. Quantification of HSA in complex biofluids, such as blood serum and urine, was also accomplished using these probes. The high selectivity of some of the probes towards HSA over the homologous BSA allowed the discrimination of these two proteins. The preferred binding location of the probes was the hemin binding site and the detection mechanism was identified as the restriction of intramolecular rotation. Additionally, a prototype of a smartphone-integrated point-of-care device was also fabricated to demonstrate the feasibility of utilizing these probes in clinical settings.

中文翻译：

基于 1,4-二氢吡啶的 FA1 位点特异性荧光探针，用于选择性检测和定量生物体液中的 HSA 水平

人血清白蛋白 (HSA) 是一种多功能循环蛋白，对于许多生理过程至关重要，包括胶体渗透压维持、配体/药物结合和转运、抗氧化活性等。在多种临床疾病中已报道生物体液中 HSA 水平异常，这使得它是早期诊断的潜在生物标志物。低血清白蛋白水平与 ICU 患者的长期和短期死亡率增加有关。因此，定量血清和尿液等生物体液中的 HSA 为早期识别潜在临床状况和评估危险因素提供了一种便捷的方法。在此，我们报告了一系列用于检测和定量生物体液中 HSA 的荧光 1,4-二氢吡啶 (DHP) 衍生物。它们对 HSA 的反应可以通过改变 DHP 环 C-4 和N -1 上的取代基来调节。根据取代基的性质，它们会产生低纳摩尔或亚纳摩尔水平 LoD 的开启或比率响应。通过在N取代基上引入手性中心获得的一对对映体强调了立体化学在 HSA-配体相互作用中的重要性。还使用这些探针完成了复杂生物流体（例如血清和尿液）中 HSA 的定量。一些探针对 HSA 相对于同源 BSA 的高选择性使得能够区分这两种蛋白质。探针的优选结合位置是氯高铁血红素结合位点，检测机制被确定为限制分子内旋转。此外，还制作了智能手机集成护理点设备的原型，以证明在临床环境中使用这些探针的可行性。

更新日期：2024-07-30

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