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Re-engineering of peptides with high binding affinity to develop an advanced electrochemical sensor for colon cancer diagnosis
Analytica Chimica Acta ( IF 5.7 ) Pub Date : 2021-02-01 , DOI: 10.1016/j.aca.2020.11.011
Chae Hwan Cho , Ji Hong Kim , Jayoung Kim , Jong Won Yun , Tae Jung Park , Jong Pil Park

Colorectal cancer (CRC) develops from polyps in the inner large intestine or rectum and an increasing incidence and high mortality rate has been observed in humans. Currently, colonoscopy is the preferred modality for early CRC diagnosis. However, this technique has several limitations, such as high medical costs and intricate procedures, leading to increasing demands for the development of a new, simple, and affordable diagnostic method. In this study, an advanced electrochemical biosensor based on rationally designed affinity peptides was developed for discriminating adenoma to carcinoma progression. Amino acid-substituted and rationally designed synthetic peptides (BP3-1 to BP3-8) based on in silico modeling studies were chemically synthesized, and covalently immobilized onto a gold electrode using aromatic ring compounds through surface chemistry techniques. The binding performance of the developed sensor system was observed using square wave voltammetry (SWV). The peptide BP3-2 was selected depending on its relative binding affinity; SWV indicated the limit of detection of BP3-2 for LRG1 to be 0.025 μg/mL. This sensor could distinguish the adenoma-carcinoma transition with improved binding abilities (specificity and selectivity), and stability in plasma samples spiked with LRG1 and real samples from patients with CRC. These results indicate that this electrochemical sensor system can be used for early monitoring of the colorectal adenoma to carcinoma progression.

中文翻译:

重新设计具有高结合亲和力的肽以开发用于结肠癌诊断的先进电化学传感器

结直肠癌 (CRC) 由大肠或直肠内的息肉发展而来,并且在人类中观察到发病率增加和死亡率高。目前,结肠镜检查是早期 CRC 诊断的首选方式。然而,这种技术有几个限制,例如高昂的医疗成本和复杂的程序,导致对开发一种新的、简单的、负担得起的诊断方法的需求不断增加。在这项研究中,开发了一种基于合理设计的亲和肽的先进电化学生物传感器,用于区分腺瘤与癌进展。基于计算机模拟研究的氨基酸取代和合理设计的合成肽(BP3-1 到 BP3-8)是化学合成的,并使用芳香环化合物通过表面化学技术共价固定在金电极上。使用方波伏安法 (SWV) 观察开发的传感器系统的结合性能。根据其相对结合亲和力选择肽 BP3-2;SWV 表明 LRG1 的 BP3-2 检测限为 0.025 μg/mL。该传感器可以通过提高的结合能力(特异性和选择性)以及掺入 LRG1 的血浆样品和来自 CRC 患者的真实样品的稳定性来区分腺瘤-癌转变。这些结果表明该电化学传感器系统可用于大肠腺瘤到癌进展的早期监测。根据其相对结合亲和力选择肽 BP3-2;SWV 表明 LRG1 的 BP3-2 检测限为 0.025 μg/mL。该传感器可以通过提高的结合能力(特异性和选择性)以及掺入 LRG1 的血浆样品和来自 CRC 患者的真实样品的稳定性来区分腺瘤-癌转变。这些结果表明该电化学传感器系统可用于大肠腺瘤到癌进展的早期监测。根据其相对结合亲和力选择肽 BP3-2;SWV 表明 LRG1 的 BP3-2 检测限为 0.025 μg/mL。该传感器可以通过提高的结合能力(特异性和选择性)以及掺入 LRG1 的血浆样品和来自 CRC 患者的真实样品的稳定性来区分腺瘤-癌转变。这些结果表明该电化学传感器系统可用于大肠腺瘤到癌进展的早期监测。加入 LRG1 的血浆样品和来自 CRC 患者的真实样品的稳定性和稳定性。这些结果表明该电化学传感器系统可用于大肠腺瘤到癌进展的早期监测。加入 LRG1 的血浆样品和来自 CRC 患者的真实样品的稳定性和稳定性。这些结果表明该电化学传感器系统可用于大肠腺瘤到癌进展的早期监测。
更新日期:2021-02-01
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