Water‐Soluble Melanin–Protein–Fe/Cu Conjugates Derived from Norepinephrine as Reliable Models for Neuromelanin of Human Brain Locus Coeruleus. (24th June 2022)

• Record Type: Journal Article
• Authors: Capucciati, Andrea; Monzani, Enrico; Sturini, Michela; Nicolis, Stefania; Zucca, Fabio A.; Bubacco, Luigi; Bortolus, Marco; Zecca, Luigi; Casella, Luigi
• Is Part Of: Angewandte Chemie. Volume 134:Number 32(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-24
• Subjects: Bioinorganic Chemistry -- Copper -- Dopamines -- Iron -- Neuromelanin; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202204787
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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 1 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 III 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 II centers. These features parallel the EPR behavior of NM from locus coeruleus . The spectral data indicate that Fe III is bound to the melanic fraction, whereas Cu II is bound on the protein fibrils, suggesting that the Fe‐Cu clusters occur at the interface between the two components of the synthetic NMs. Abstract : Melanin–protein conjugates derived from norepinephrine fibrillar β‐lactoglobulin were synthesized as soluble models of neuromelanin from human brain locus coeruleus . This pigment contains a significant amount of iron and copper. The synthetic models show that the two metals exhibit a strong tendency to remain coupled to each other in dinuclear or multinuclear aggregates.