Department of Chemistry, University of Pavia, Via Taramelli 12, 27100, Pavia, Italy.
Institute of Biomedical Technologies, National Research Council of Italy, Via Cervi 93, 20054, Segrate (Milan), Italy.
Angew Chem Int Ed Engl. 2022 Aug 8;61(32):e202204787. doi: 10.1002/anie.202204787. Epub 2022 Jun 24.
Water-soluble melanin-protein-Fe/Cu conjugates derived from norepinephrine and fibrillar β-lactoglobulin are reliable models for neuromelanin (NM) of human brain locus coeruleus. Both iron and copper promote catecholamine oxidation and exhibit strong tendency to remain coupled in oligonuclear aggregates. The Fe-Cu clusters are EPR silent and affect the H NMR spectra of the conjugates through a specific sequence of signals. Derivatives containing only Fe or Cu exhibit different NMR patterns. The EPR spectra show weak signals of paramagnetic Fe in conjugates containing Fe or mixed Fe-Cu sites due to small amounts of mononuclear centers. The latter derivatives exhibit EPR signals for isolated Cu centers. These features parallel the EPR behavior of NM from locus coeruleus. The spectral data indicate that Fe is bound to the melanic fraction, whereas Cu is bound on the protein fibrils, suggesting that the Fe-Cu clusters occur at the interface between the two components of the synthetic NMs.
由去甲肾上腺素和纤维状β-乳球蛋白衍生的水溶性黑色素-蛋白-Fe/Cu 配合物是人类脑蓝斑核神经黑色素 (NM) 的可靠模型。铁和铜都促进儿茶酚胺的氧化，并表现出强烈的倾向，以保持在寡核聚集体中结合。Fe-Cu 簇是 EPR 无信号的，并通过特定的信号序列影响配合物的 1H NMR 光谱。仅含有 Fe 或 Cu 的衍生物表现出不同的 NMR 图谱。由于单核中心的含量很少，因此含有 Fe 或混合 Fe-Cu 位点的配合物中的 EPR 光谱显示出顺磁 Fe 的弱信号。后一种衍生物表现出孤立的 Cu 中心的 EPR 信号。这些特征与蓝斑核 NM 的 EPR 行为平行。光谱数据表明 Fe 与黑色素部分结合，而 Cu 与蛋白质纤维结合，这表明 Fe-Cu 簇发生在合成 NM 的两个组成部分之间的界面处。
