Complexes of aluminium with peptide ligands: A fourier transform IR spectroscopic study

Aluminium has been recognized to be a neurotoxic agent and a risk factor in Alzheimer's disease and other neuronal dysfunctions. CD spectroscopic studies on two synthetic fragments of the human neurofilament protein midsized subunit (NF-M), and their alanine-for-serine-substituled and /or serine-phosphorylated derivatives showed the formation of stable, citric acid resistant complexes of Al³⁺with peptide ligands [M. Hollósi, Z.M. Shen, A. Perczel, and G.D. Fasman (1994) Proc. Natl. Acad. Sci. USA, vol. 9 , pp.4902-4906]. In the case of Ser-phosphorylated fragments, aβ-sheet inducing effect of Ca²⁺ and Al³⁺ ions was observed. However, the serine-containing parent peptides, NF-M 13 (KSPVPKSPVEEKG) and NF-M 17 (EEKGKSPVPKSPVEEKG), failed to show CD spectral changes reflecting β-sheet formation upon addition of Al³⁺ ions. On the basis of the amide I region of the Fourier transform ir spectra, in triftuoroethanol, the peptide backbone of NF-M17 and NF-M17 (A⁶A¹¹) shows marked changes in the presence ofAl³⁺. The most significant spectral differences are seen in the car-boxyl region (> 1700 cm^?l). The high-frequency component bands above 1760 cm^?1 in both spectra belong to the C? O of undissociated CF₃COOH. Another strong band at 1710 cm^?1 which appears only in the spectrum of NF-Ml 7 (A⁶A¹¹)(NF-M17 with Ser⁶ andSer¹¹ replaced by Ala) can be assigned to the side chain or C-terminal COOH groups. The differential proton-ation state of the carboxyl groups in the two peptides suggests the format ion ofAl³⁺ complexes of different structure and stability. The Al³⁺ complex ofNF-Ml 7 (A⁶A¹¹) is likely less stable, or one or more of the carboxylates are not coordinated to the Al³⁺ and thus can serve as a base to bind the liberated protons. In NF-M17 the OH groups of serines facilitate the formation of type [Al-pep(H_-1)] complexes with the involvement of all carboxylategroups in the molecule. The relevance of intramolecular and intermolecular Al³⁺ binding to the controversial biological role of aluminium is also discussed. © 1995 John Wiley & Sons, Inc.