Ligand-Induced Flocculation of Neurotoxic Fibrillar Abeta(1-42) by Noncovalent Crosslinking
Aggregation of the amyloid- (A) peptides has a pivotal role in Alzheimers disease (AD). Small molecules and short peptides/peptidomimetics can exert their full protective effects against A within a short time-frame, but the exact mechanism of action is unclear. Time-dependent NMR spectroscopic bindi...
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| Dokumentumtípus: | Cikk |
| Megjelent: |
Wiley-VCH Verlag GmbH & Co. KGaA
2008
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| Sorozat: | CHEMBIOCHEM
9 No. 5 |
| doi: | 10.1002/cbic.200700351 |
| mtmt: | 1115201 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/7559 |
| Tartalmi kivonat: | Aggregation of the amyloid- (A) peptides has a pivotal role in Alzheimers disease (AD). Small molecules and short peptides/peptidomimetics can exert their full protective effects against A within a short time-frame, but the exact mechanism of action is unclear. Time-dependent NMR spectroscopic binding and replacement experiments were carried out for peptide LPFFD and thioflavine T (ThT) on neurotoxic fibrillar A(1-42), which revealed transient binding behavior for both compounds, and complex time-dependent features in the replacement experiments. The results of particle size measurements through the use of diffuse light-scattering and transmission electron microscopy support the conclusions that the studied ligands induced interfibrillar association on a short timescale, which explains the NMR spectroscopic binding and replacement results. -Potential measurements revealed a slightly increased electrostatic stability of the A fibrils upon ligand binding; this suggests that the interfibrillar assembly is driven by specific noncovalent cross-linking interactions. A specific surface and mobility decrease due to the ligand-induced flocculation of the A fibrils can explain the neuroprotective effects. |
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| Terjedelem/Fizikai jellemzők: | 748-757 |
| ISSN: | 1439-4227 |