Authors: Emanuele Ferrari Mireille Engelen Enrico Monzani Michela Sturini Stefania Girotto Luigi Bubacco Luigi Zecca Luigi Casella
Publish Date: 2012/10/31
Volume: 18, Issue: 1, Pages: 81-93
Abstract
Elucidating the structure and biosynthesis of neuromelanin NM would be an important step towards understanding its putative role in the pathogenesis of Parkinson’s disease A useful complement to studies aimed at unraveling the origin and properties of this essentially insoluble natural substance is the preparation of synthetic derivatives that resemble NM With this aim in mind watersoluble conjugates between dopaminederived melanin and bovine serum albumin BSA were synthesized Melanin–BSA adducts were prepared with both eumelanic oligomers obtained through the oxidative polymerization of dopamine and pheomelanic oligomers obtained under the same conditions from dopamine and cysteine Iron ions were added during the synthesis to understand the interaction between the pigment and this metal ion as the NM in neurons in several human brain regions contains significant amounts of iron The structures of the conjugates were analyzed by 1H NMR spectroscopy and controlled proteolysis/MS experiments The binding of ironIII ions was evaluated by ICP analysis and EPR spectroscopy The EPR signal from bound ironIII indicated highspin octahedral sites and as also seen for NM the signal is coupled to a signal from a radical associated with the melanic components of the conjugates However the intensity of the EPR signal from iron suggested a reduced fraction of the total iron indicating that most of the iron is strongly coupled in clusters within the matrix The amount of paramagnetic mononuclear ironIII was greater in the pheomelanin–BSA conjugates suggesting that iron clustering is reduced in the sulfurcontaining pigment Thus the melanin–BSA conjugates appear to be good models for the natural pigment
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