ISSN:
0006-3525
Schlagwort(e):
Chemistry
;
Polymer and Materials Science
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Chemie und Pharmazie
Notizen:
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.
Zusätzliches Material:
2 Ill.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/bip.360360311
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