Interaction of synthetic Alzheimerβ-protein-derived analogs with aqueous aluminum: A low-field27Al NMR investigation

Abstract

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.

The alum-processing mechanism attenuating toxicity of Araceae Pinellia ternata and Pinellia pedatisecta

“…coordination during raphides processing with alum Two kinds of raphides of P. ternata and P. pedatisecta were taken in the right amount; 8 % alum solution was added to dilute 4 mg/mL solution, centrifuged to get supernatant after 48 h for 27 Al-NMR analysis (Vyas and Duffy 1995).…”

Aluminum modulation of proteolytic activities

“…In this context the aluminum role could be envisaged at different levels. First, the metal could affect the formation of amyloid peptides through a positive modulation of the proteolytic processes involved in the b-amyloid precursor processing; then it could bind to the so-formed peptides, promoting their aggregation and precipitation and accelerating the formation of the neuritic plaque [38]. On the whole, aluminum produces an overall activating effect on achymotrypsin, which can be observed at physiological concentration of the metal (estimated to be about 10 mM), thus reinforcing the idea of a key role of this ion in different pathological processes, such as the formation of amyloid plaques.…”

Aluminum inhibits proteolytic degradation of amyloid β peptide by cathepsin D: A potential link between aluminum accumulation and neuritic plaque deposition

“…that of the lysosomal fraction in the brain). Recently, Vyas et al [47] [20,21]. Therefore, it is possible that the steric interaction between Al and Ab peptides may affect the digestion of Ab peptides by disturbing the cleavage sites for cathepsin D, even before aggregation of the Ab peptide occurs.…”

“…that of the lysosomal fraction in the brain). Recently, Vyas et al [47] indicated using 27 Al nuclear magnetic resonance spectroscopy and amino acid sequencing of Ab peptides in the presence of Al that Al 3+ ions could interact with Ab 1-40 and Ab 6-25 peptides. Their data also showed the possibility that Asp 7 , His 14 , and Asp 23 have undergone steric interference associated with aqueous Al 3+ to form a relatively stable complex.…”