Human amylin (hIAPP) is one of a number of different peptides known to be responsible for the formation of amyloid fibrils in the pancreas of subjects with Type 2 diabetes mellitus. It was recognized that metal ions such as Cu(II) are implicated in the aggregation process of amyloidogenic peptides. However, the role of Cu(II) ions in the aggregation and dyshomeostasis of amylin has been controversial. Considering that most of the research reported in the literature pertain to the interactions between Cu(II) and amylin, we thought of interest to compare the interactions of Cu(II) and Cu(I) ions with amylin by electrospray ionization (ESI) mass spectrometry and collisional experiments, to elucidate possible differences in structural aspects of the complexes so formed. The ESI mass spectra of solutions containing hIAPP and Cu(I) or Cu(II) ions show the formation of hIAPP–Cu complexes. In both cases, M + Cu ions with three and four positive charges are detected. However, a series of fragment ions, absent in the ESI spectrum of untreated hIAPP, become detectable. Some of them are common for both Cu(I) and Cu(II) complexes, whereas others are specific for the complexes containing Cu in different oxidation states. Some fragments imply the involvement of residues His18, Ser19, Ser20, Asn21, and Asn22 in the complex formation, but the detection of the fragment b₂₂³⁺ indicates the presence of copper ions in a different position. This suggests different interaction sites between Cu(II) and Cu(I) and hIAPP. In contrast to Cu(II) complex, in the Cu(I) complex, some peculiar structures are present, corresponding to the cleavage of Asn–Asn peptidic bond and to [b₃₀ + Cu(I)]⁴⁺ and [b₂₈ + Cu(I)]⁴⁺ species. These results are in agreement with the coordination vacancy in [Cu(I)–(peptide)] species, which promotes Cu(I) interaction with additional neighboring donors (mainly N-histidine, and also S-methionine or other groups depending on the peptide conformation) through formation of trigonal T-shaped intermediates.

中文翻译：

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胰淀素与Cu(II)和Cu(I)配合物的电喷雾电离研究

人淀粉样蛋白 (hIAPP) 是已知负责在患有 2 型糖尿病的受试者的胰腺中形成淀粉样蛋白原纤维的多种不同肽之一。人们认识到金属离子如 Cu(II) 与淀粉样肽的聚集过程有关。然而，Cu(II) 离子在胰淀素的聚集和失调中的作用一直存在争议。考虑到文献中报道的大多数研究都与 Cu(II) 和胰淀素之间的相互作用有关，我们认为有兴趣通过电喷雾电离 (ESI) 质量比较 Cu(II) 和 Cu(I) 离子与胰淀素的相互作用光谱法和碰撞实验，以阐明如此形成的配合物在结构方面可能存在的差异。含有 hIAPP 和 Cu(I) 或 Cu(II) 离子的溶液的 ESI 质谱显示了 hIAPP-Cu 复合物的形成。在这两种情况下，都检测到带有三个和四个正电荷的 M + Cu 离子。然而，在未经处理的 hIAPP 的 ESI 光谱中不存在的一系列碎片离子变得可检测到。其中一些对于 Cu(I) 和 Cu(II) 复合物是常见的，而另一些则是特定于含有不同氧化态 Cu 的复合物。一些片段暗示残基His18、Ser19、Ser20、Asn21和Asn22参与复合物形成，但片段b的检测 其中一些对于 Cu(I) 和 Cu(II) 复合物是常见的，而另一些则是特定于含有不同氧化态 Cu 的复合物。一些片段暗示残基His18、Ser19、Ser20、Asn21和Asn22参与复合物形成，但片段b的检测 其中一些对于 Cu(I) 和 Cu(II) 复合物是常见的，而另一些则是特定于含有不同氧化态 Cu 的复合物。一些片段暗示残基His18、Ser19、Ser20、Asn21和Asn22参与复合物形成，但片段b的检测₂₂ ³⁺表示在不同位置存在铜离子。这表明 Cu(II) 和 Cu(I) 和 hIAPP 之间的相互作用位点不同。与Cu(II)配合物相反，在Cu(I)配合物中，存在一些特殊的结构，对应于Asn-Asn肽键的断裂和[b ₃₀  + Cu(I)] ⁴⁺和[b ₂₈  + Cu(I)] ⁴⁺种。这些结果与 [Cu(I)–(peptide)] 物种中的配位空位一致，这促进了 Cu(I) 与其他相邻供体（主要是 N-组氨酸，以及 S-甲硫氨酸或其他基团，取决于肽构象）通过形成三角 T 形中间体。