Interactions of Al(III) with phosphorylated amino acids

In order to assess the Al(III)-binding abilities of phosphorylated proteins and peptides, the interactions of AI(III) with the building blocks O-phosphoserine (PSer) and O-phosphotyrosine (PTyr) were studied. pi-I-metric and P-31 NMR measurements were carried out to determine the stoichiometries and stability constants of the complexes formed, and to establish the most probable binding sites of the metal ion. PSer was found to bind Al(III) in a monodentate manner at the phosphate moiety, and in a tridentate manner with the simultaneous coordination of all donor groups. PTyr binds P-I(III) only at the separate phosphate function. Citric acid (Cit) proved to be a stronger Al(III) binder at the physiological pH, though, it was able to displace PSer only in a rather slow process through formation of the trinuclear species Al-3(Cit)(3)(OH). The results were used to evaluate the potential role of Al(III) in inducing the formation of neurofilamentous aggregates in neurological disorders. (C) 1998 Elsevier Science Inc. All rights reserved.