Designed Multifunctional Isopeptide for Enhanced Annexin A1 Biosensing Based on Peptide–Protein Interactions in Human Blood,Analytical Chemistry

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Designed Multifunctional Isopeptide for Enhanced Annexin A1 Biosensing Based on Peptide–Protein Interactions in Human Blood
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-05-28 , DOI: 10.1021/acs.analchem.3c01144
Rui Han ₁ , Yang Li ₁ , Wenjie Hou ₁ , Caifeng Ding ₁ , Xiliang Luo ₁

Affiliation

Specific peptide–protein interactions play an important role in biosensing systems based on functional peptides; however, the non-specific interactions with unrelated biomolecules and poor proteolytic stability restrict the clinical application of natural peptides. Here, we leveraged a self-designed multifunctional isopeptide (MISP) to construct an electrochemical biosensing platform for annexin A1 (ANXA1) detection in human blood. The MISP was designed to contain two parts: an antifouling cyclotide cyclo-C(EK)₄ and a d-amino acid-containing carbohydrate-mimetic recognizing peptide IF-7 (D-IF7) connected by the isopeptide bond. We have discussed the properties of the cyclotide and illustrated its unique advantage over the natural linear antifouling peptides by molecular dynamics simulations, and the results were further confirmed by dissipative quartz crystal microbalance (QCM-D). In addition, through electrochemical experiments and fluorescence imaging experiments, we demonstrated that the MISP-based biosensor possessed excellent antifouling ability and proteinase hydrolysis stability. Interestingly, the assaying results of the MISP-biosensor were consistent with those of the commercial ANXA1 kits in a variety of healthy and ANXA1-upregulated clinical blood samples, and, more importantly, for the analysis of blood samples with lower ANXA1 expressions, the sensing capability of the biosensor was greatly superior to that of the kits because of the lower detection limit of the MISP-biosensor. This biosensing platform based on the designed MISP offers enormous potential for achieving accurate biomarker detection with robust operation in complex biological samples.

中文翻译：

基于人体血液中肽-蛋白质相互作用设计的多功能异肽用于增强膜联蛋白 A1 生物传感

特定的肽-蛋白质相互作用在基于功能肽的生物传感系统中起着重要作用；然而，与无关生物分子的非特异性相互作用和较差的蛋白水解稳定性限制了天然肽的临床应用。在这里，我们利用自行设计的多功能异肽 (MISP) 构建了用于检测人血液中膜联蛋白 A1 (ANXA1) 的电化学生物传感平台。MISP 被设计为包含两部分：防污环肽 cyclo-C(EK) ₄和d- 含氨基酸的碳水化合物模拟识别肽 IF-7 (D-IF7) 通过异肽键连接。我们讨论了环肽的性质，并通过分子动力学模拟说明了其相对于天然线性防污肽的独特优势，并通过耗散石英晶体微天平（QCM-D）进一步证实了该结果。此外，通过电化学实验和荧光成像实验，我们证明了基于MISP的生物传感器具有优异的防污能力和蛋白酶水解稳定性。有趣的是，MISP-生物传感器的检测结果与商业 ANXA1 试剂盒在各种健康和 ANXA1 上调的临床血液样本中的检测结果一致，更重要的是，对于 ANXA1 表达较低的血液样本的分析，由于 MISP 生物传感器的检测限较低，因此生物传感器的传感能力大大优于试剂盒。这种基于设计的 MISP 的生物传感平台为实现准确的生物标志物检测提供了巨大的潜力，并在复杂的生物样本中稳健运行。

更新日期：2023-05-28

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