Sittiwanichai Sirin, Niramitranon Jitti, Japrung Deanpen, Pongprayoon Prapasiri
Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok 10900, Thailand.
Department of Computer Engineering, Kasetsart University, Chatuchak, Bangkok 10900, Thailand.
ACS Omega. 2023 Jun 6;8(24):21862-21870. doi: 10.1021/acsomega.3c01595. eCollection 2023 Jun 20.
Diabetes mellitus is a chronic metabolic disease involving continued elevated blood glucose levels. It is a leading cause of mortality and reduced life expectancy. Glycated human serum albumin (GHSA) has been reported to be a potential diabetes biomarker. A nanomaterial-based aptasensor is one of the effective techniques to detect GHSA. Graphene quantum dots (GQDs) have been widely used in aptasensors as an aptamer fluorescence quencher due to their high biocompatibility and sensitivity. GHSA-selective fluorescent aptamers are first quenched upon binding to GQDs. The presence of albumin targets results in the release of aptamers to albumin and consequently fluorescence recovery. To date, the molecular details on how GQDs interact with GHSA-selective aptamers and albumin remain limited, especially the interactions of an aptamer-bound GQD (GQDA) with an albumin. Thus, in this work, molecular dynamics simulations were used to reveal the binding mechanism of human serum albumin (HSA) and GHSA to GQDA. The results show the rapid and spontaneous assembly of albumin and GQDA. Multiple sites of albumins can accommodate both aptamers and GQDs. This suggests that the saturation of aptamers on GQDs is required for accurate albumin detection. Guanine and thymine are keys for albumin-aptamer clustering. GHSA gets denatured more than HSA. The presence of bound GQDA on GHSA widens the entrance of drug site I, resulting in the release of open-chain glucose. The insight obtained here will serve as a base for accurate GQD-based aptasensor design and development.
糖尿病是一种慢性代谢疾病，其特征是血糖水平持续升高。它是导致死亡和预期寿命缩短的主要原因。据报道，糖化人血清白蛋白（GHSA）是一种潜在的糖尿病生物标志物。基于纳米材料的适体传感器是检测GHSA的有效技术之一。由于其高生物相容性和灵敏度，石墨烯量子点（GQDs）已被广泛用作适体荧光猝灭剂用于适体传感器中。GHSA选择性荧光适体在与GQDs结合时首先被猝灭。白蛋白靶标的存在导致适体从GQDs释放到白蛋白上，从而使荧光恢复。迄今为止，关于GQDs如何与GHSA选择性适体和白蛋白相互作用的分子细节仍然有限，特别是适体结合的GQD（GQDA）与白蛋白的相互作用。因此，在这项工作中，使用分子动力学模拟来揭示人血清白蛋白（HSA）和GHSA与GQDA的结合机制。结果表明白蛋白和GQDA能快速自发组装。白蛋白的多个位点可以同时容纳适体和GQDs。这表明为了准确检测白蛋白，需要使GQDs上的适体饱和。鸟嘌呤和胸腺嘧啶是白蛋白-适体聚集的关键。与HSA相比，GHSA更容易变性。GHSA上结合的GQDA的存在会拓宽药物位点I的入口，导致开链葡萄糖的释放。这里获得的见解将为基于GQD的适体传感器的准确设计和开发奠定基础。
