Cyclopeptides hold significant relevance in various fields of science and medicine, due to their unique structural properties and diverse biological activities. Cyclic peptides, characterized by intrinsically higher conformational order, exhibit remarkable stability and resistance to proteolytic degradation, making them attractive candidates for developing targeted drug delivery systems. The aim of this work is to elucidate the unique coordination properties of the multi-His cyclic peptide with c(HDHKHPHHKHHP) sequence (HDCP – heterodomain cyclopeptide). This peptide, indeed, is able to form homo- and hetero-dinuclear complexes in a wide pH range, being thus a good chelator for Cu(II) ions. Herein, we present the results of a combined study, involving potentiometric, spectroscopic (UV–Vis, CD, and EPR), and computational investigations, on its coordination properties. To better understand the interaction pattern with Cu(II) metal ions, two other peptides, each one bearing only one of the two binding domains of HDCP are also considered in this study: c(HDHKHPGGKGGP) = CP1, c(GKGGKPHHKHHP) = CP2, which share sequence fragments of HDCP and allow separate investigations of its coordination domains.

中文翻译：

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多组氨酸环肽异域对 Cu(II) 离子结合能力的详细研究

环肽由于其独特的结构特性和多样化的生物活性，在科学和医学的各个领域具有重要的相关性。环肽的特点是本质上具有更高的构象顺序，表现出显着的稳定性和对蛋白水解降解的抵抗力，使它们成为开发靶向药物递送系统的有吸引力的候选者。这项工作的目的是阐明多组氨酸环肽与 c(HDHKHPHHKHHP) 序列（HDCP – 异域环肽）的独特配位特性。事实上，这种肽能够在较宽的 pH 范围内形成同源和异源双核复合物，因此是 Cu(II) 离子的良好螯合剂。在此，我们介绍了对其配位特性的综合研究结果，包括电位测定、光谱（UV-Vis、CD 和 EPR）和计算研究。为了更好地了解与 Cu(II) 金属离子的相互作用模式，本研究还考虑了另外两种肽，每种肽仅带有 HDCP 的两个结合域之一：c(HDHKHPGGKGGP) = CP1，c(GKGGKPHHKHHP) = CP2 ，它们共享 HDCP 的序列片段并允许对其协调域进行单独研究。