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.