CNRS, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, BP 44099, CEDEX 4, 31077 Toulouse, France.
Molecules. 2022 Nov 15;27(22):7903. doi: 10.3390/molecules27227903.
Amino-terminal Cu and Ni (ATCUN) binding sequences are widespread in the biological world. Here, we report on the study of eight ATCUN peptides aimed at targeting copper ions and stopping the associated formation of reactive oxygen species (ROS). This study was actually more focused on Cu(Aβ)-induced ROS production in which the Aβ peptide is the "villain" linked to Alzheimer's disease. The full characterization of Cu binding to the ATCUN peptides, the Cu extraction from Cu(Aβ), and the ability of the peptides to prevent and/or stop ROS formation are described in the relevant biological conditions. We highlighted in this research that all the ATCUN motifs studied formed the same thermodynamic complex but that the addition of a second histidine in position 1 or 2 allowed for an improvement in the Cu uptake kinetics. This kinetic rate was directly related to the ability of the peptide to stop the Cu(Aβ)-induced production of ROS, with the most efficient motifs being HWHG and HGHW.
氨基末端铜和镍（ATCUN）结合序列广泛存在于生物界。在这里，我们报告了对 8 种 ATCUN 肽的研究，旨在靶向铜离子并阻止相关活性氧（ROS）的形成。这项研究实际上更侧重于 Cu(Aβ)诱导的 ROS 产生，其中 Aβ肽是与阿尔茨海默病相关的“罪魁祸首”。在相关的生物学条件下，我们详细描述了 Cu 与 ATCUN 肽的结合、Cu(Aβ)中 Cu 的提取以及肽预防和/或阻止 ROS 形成的能力。在这项研究中，我们强调所有研究的 ATCUN 基序都形成了相同的热力学复合物，但在第 1 位或第 2 位添加第二个组氨酸可以提高 Cu 的摄取动力学。这种动力学速率与肽阻止 Cu(Aβ)诱导的 ROS 产生的能力直接相关，其中最有效的基序是 HWHG 和 HGHW。
