Institute of Crystallography, National Research Council of Italy (CNR), P. Gaifami 18, 95126 Catania, Italy.
Department of Chemical Sciences, University of Catania, A. Doria 6, 95125 Catania, Italy.
Molecules. 2023 Sep 20;28(18):6724. doi: 10.3390/molecules28186724.
Neurodegenerative diseases affect millions of people worldwide. The failure of the enzymatic degradation, the oxidative stress, the dyshomeostasis of metal ions, among many other biochemical events, might trigger the pathological route, but the onset of these pathologies is unknown. Multi-target and multifunctional molecules could address several biomolecular issues of the pathologies. The tripeptide GHK, a bioactive fragment of several proteins, and the related copper(II) complex have been largely used for many purposes, from cosmetic to therapeutic applications. GHK derivatives were synthesized to increase the peptide stability and improve the target delivery. Herein we report the synthesis of a new biotin-GHK conjugate (BioGHK) through orthogonal reactions. BioGHK is still capable of coordinating copper(II), as observed by spectroscopic and spectrometric measurements. The spectroscopic monitoring of the copper-induced ascorbate oxidation was used to measure the antioxidant activity Cu(II)-BioGHK complex, whereas antiglycant activity of the ligand towards harmful reactive species was investigated using MALDI-TOF. The affinity of BioGHK for streptavidin was evaluated using a spectrophotometric assay and compared to that of biotin. Finally, the antiaggregant activity towards amyloid-β was evaluated using a turn-on fluorescent dye. BioGHK could treat and/or prevent several adverse biochemical reactions that characterize neurodegenerative disorders, such as Alzheimer's disease.
神经退行性疾病影响着全球数百万人。酶降解的失败、氧化应激、金属离子的动态失衡，以及许多其他生化事件，可能引发病理途径，但这些病理的发病机制尚不清楚。多靶点和多功能分子可以解决病理的多个生物分子问题。三肽 GHK 是几种蛋白质的生物活性片段，以及相关的铜（II）配合物已被广泛用于许多目的，从美容到治疗应用。为了增加肽的稳定性并改善靶标递呈，已经合成了 GHK 的衍生物。本文通过正交反应报告了一种新的生物素-GHK 缀合物（BioGHK）的合成。通过光谱和光谱测量观察到，BioGHK 仍然能够与铜（II）配位。通过铜诱导抗坏血酸氧化的光谱监测，测量了铜（II）-BioGHK 配合物的抗氧化活性，而使用 MALDI-TOF 研究了配体对有害活性物质的抗糖化活性。使用分光光度法评估了 BioGHK 与链霉亲和素的亲和力，并与生物素进行了比较。最后，使用荧光染料的开/关法评估了 BioGHK 对淀粉样蛋白-β的抗聚集活性。BioGHK 可以治疗和/或预防几种神经退行性疾病（如阿尔茨海默病）的特征性不良生化反应。
