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Metal ions like Cu(II) and Zn(II) are accumulated in Alzheimer's disease amyloid plaques. The amyloid-beta (A beta) peptide involved in the disease interacts with these metal ions at neutral pH via ligands provided by the N-terminal histidines and the N-terminus. The present study uses high-resolution NMR spectroscopy to monitor the residue-specific interactions of Cu(II) and Zn(II) with N-15- and C-13,N-15-labeled A beta(1-40) peptides at varying pH levels. At pH 7.4 both ions bind to the specific ligands, competing with one another. At pH 5.5 Cu(II) retains its specific histidine ligands, while Zn(II) seems to lack residue-specific interactions. The low pH mimics acidosis which is linked to inflammatory processes in vivo. The results suggest that the cell toxic effects of redox active Cu(II) binding to AD may be reversed by the protective activity of non-redox active Zn(II) binding to the same major binding site under non-acidic conditions. Under acidic conditions, the protective effect of Zn(II) may be decreased or changed, since Zn(II) is less able to compete with Cu(II) for the specific binding site on the AD peptide under these conditions., AuthorCount:5

Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information

Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information

Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information

Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information

Oligosaccharides (carbohydrates) are a large class of biological molecules that are important as energy sources in the human body and have enormously varied biological functions. It is generally believed that biological activities of carbohydrates are related to their internal dynamics. The dynamic properties of some oligosaccharides in solution are studied in this thesis, by NMR relaxation. We have employed relaxation interference effects to investigate the conformational dynamics within oligosaccharides (in-tramolecular dynamics) and paramagnetic relaxation enhancement (PRE) as an experimental tool to study intermolecular dynamics. Most of the thesis concerns the dynamics of the methylene group in the two possibly mobile parts of the oligosaccharide: in the exocyclic hydroxymethyl moiety and in the glycosidic linkage position. To perform conformational dynamic studies, the more traditional auto-relaxation pa-rameters are combined with the relaxation interference terms or the cross-correlated relaxation rates (CCRRs). Some experimental schemes based on the initial-rate technique were developed for measuring CCRRs. The techniques are useful for labelled sugars as well as naturally abundant ones. Furthermore, various dynamical models ranging from the Lipari–Szabo approach to several more informative and complicated models such as the two-site jump model, restricted internal rotation and slowly relaxing local structure (SRLS), have been employed to interpret our experimental data. We have combined and com-pared different models; we have also developed a novel approach to existing models, by scaling dipolar coupling constants (DCC), to extract the dynamic behaviour and structural properties of the system. We found that the auto- and cross-correlated relaxation data analyses yield a consistent picture of the dynam-ics in all cases. Additionally, our investigations show that CCRRs are practically important for verifica-tion of certain dynamical and structural information

Part of urn:nbn:se:su:diva-8211

Part of urn:nbn:se:su:diva-8211

Part of urn:nbn:se:su:diva-8211