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淀粉样β蛋白与点击肽-卟啉共轭物相互作用的光谱研究:水溶液中Aβ肽检测的展望

A Spectroscopic Study on the Amyloid-β Interaction with Clicked Peptide-Porphyrin Conjugates: a Vision Toward the Detection of Aβ Peptides in Aqueous Solution.

作者信息

Tosto Rita, Zimbone Stefania, Sabatino Giuseppina, Di Natale Giuseppe, Laura Giuffrida Maria, Flora Tomasello Marianna, Lanzanò Luca, Campagna Tiziana, Covaceuszach Sonia, Vecchio Graziella, Pappalardo Giuseppe

机构信息

Institute of Crystallography, National Research Council, Via Paolo Gaifami 18, 95126, Catania, Italy.

International PhD School of Chemical Sciences, Department of Chemical Sciences, University of Catania, Viale Andrea Doria, 6, 95125, Catania, Italy.

出版信息

Chembiochem. 2024 Dec 2;25(23):e202400431. doi: 10.1002/cbic.202400431. Epub 2024 Nov 7.

Abstract

Alzheimer's disease (AD) is a multifactorial form of dementia mainly affecting people in the elderly, but no effective cure is available. According to the amyloid hypothesis the aggregation of Amyloid-β (Aβ) into oligomeric toxic species is believed to concur with the onset and progression of the disease heavily. By using a click chemistry approach, we conjugated a suitable designed peptide sequence to a metalloporphyrin moiety to obtain three hybrid peptide systems to be studied for their interaction with Amyloid-β peptides. The aim is to get new tools for the diagnosis and therapy in AD. The results described in this study, which were obtained through spectroscopic techniques (UV-Vis, CD, bis-Ans and intrinsic porphyrin Fluorescence), Microfluidics (GCI) and cell biology (MTT, Live cell imaging and flow cytometry), reveal interesting features about the structure-activity relationships connecting these conjugates with the interaction with Aβ, as well as on their potential use as sensing systems. In our opinion the data reported in this paper make the porphyrin-peptide conjugates highly compelling for further exploration as spectroscopic probes to detect Aβ biomarkers in biological fluids.

摘要

阿尔茨海默病(AD)是一种多因素导致的痴呆症,主要影响老年人,但目前尚无有效的治疗方法。根据淀粉样蛋白假说,淀粉样β蛋白(Aβ)聚集成寡聚毒性物质被认为与该疾病的发生和发展密切相关。通过点击化学方法,我们将一个设计合适的肽序列与金属卟啉部分偶联,得到了三个杂合肽系统,用于研究它们与淀粉样β肽的相互作用。目的是获得用于AD诊断和治疗的新工具。本研究通过光谱技术(紫外可见光谱、圆二色光谱、双-ANS和固有卟啉荧光)、微流控技术(GCI)和细胞生物学(MTT、活细胞成像和流式细胞术)获得的结果,揭示了这些偶联物与Aβ相互作用的结构-活性关系的有趣特征,以及它们作为传感系统的潜在用途。我们认为,本文报道的数据使得卟啉-肽偶联物作为检测生物流体中Aβ生物标志物的光谱探针极具进一步探索的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b8/11610669/9d318807fc0a/CBIC-25-e202400431-g008.jpg

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