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-substituted 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, a beta-sheet inducing effect of Ca2+ and Al3+ ions was observed. However, the serine-containing parent peptides, NF-M13 (KSPVPKSPVEEKG) and NF-M17 (EEKGKSPVPKSPVEEKG), failed to show CD spectral changes reflecting beta-sheet formation upon addition of Al3+ ions. On the basis of the amide I region of the Fourier transform ir spectra, in trifluoroethanol, the peptide backbone of NF-M17 and NF-M17 (A6A11) shows marked changes in the presence of Al3+. The most significant spectral differences are seen in the carboxyl region (> 1700 cm-1). 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-M17 (A6A11)(NF-M17 with Ser6 and Ser11 replaced by Ala) can be assigned to the side chain or C-terminal COOH groups. The differential protonation state of the carboxyl groups in the two peptides suggests the formation of Al3+ complexes of different structure and stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Hollósi
M
M
Deparment of Organic Chemistry, Eötvös University, Budapest, Hungary.
Holly
S
S
Majer
Z
Z
Laczkó
I
I
Fasman
G D
GD
D000535:Aluminum / Q000737:chemistry*; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
D008024:Ligands; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D010455:Peptides; D000535:Aluminum