Interaction of synthetic Alzheimer beta-protein-derived analogs with aqueous aluminum: a low-field 27Al NMR investigation.
Synthetic peptides corresponding to the soluble Alzheimer beta-protein, i.e., beta 1-40 and beta 6-25, were utilized to investigate the association of aluminum using low-field 27Al nuclear magnetic resonance (NMR) spectroscopy and reversed-phase high-performance liquid chromatography (RP-HPLC). Addition of beta 1-40 or beta 6-25 to aqueous Al3+ gives rise to a 27Al NMR signal corresponding to the association of Al3+ with the peptides; this effect is not easily reversed by EDTA. Based on the relative intensity of the Al(3+)-peptide signal between pH 4 and 6, there are at least 4 Al3+ ions associated with each peptide molecule. Microheterogeneity is observed with RP-HPLC on incubating solutions of Al3+ with beta 1-40 and beta 6-25. The 27Al NMR spectra of chromatographically pure fractions of beta 1-40 and beta 6-25 indicate that the peptide-associated Al3+ is released below pH 3.5. We propose that soluble beta 1-40 provides an anchor for Al3+ to bind, eventually leading to an increased deposition of amyloid in the Alzheimer brain.
Vyas
S B
SB
Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Alaska 99775, USA.
Duffy
L K
LK
D000535:Aluminum / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004492:Edetic Acid; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012995:Solubility
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C091513:amyloid beta-protein (6-25); D004492:Edetic Acid; D000535:Aluminum