Ryan, Timothy M. published the artcileSmall Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1-42, Application of (2R,3S,4S,5R,6S)-2-(Hydroxymethyl)-6-(octylthio)tetrahydro-2H-pyran-3,4,5-triol, the publication is Journal of Biological Chemistry (2012), 287(20), 16947-16954, database is CAplus and MEDLINE.
Amyloid fibril formation is associated with a number of debilitating systemic and neurodegenerative diseases. One of the most prominent is Alzheimer disease in which aggregation and deposition of the Aβ peptide occur. Aβ is widely considered to mediate the extensive neuronal loss observed in this disease through the formation of soluble oligomeric species, with the final fibrillar end product of the aggregation process being relatively inert. Factors that influence the aggregation of these amyloid-forming proteins are therefore very important. The authors have screened a library of 96 amphipathic mols. for effects on Aβ1-42 aggregation and self-association The authors find, using thioflavin T fluorescence and electron microscopy assays, that 30 of the mols. inhibit the aggregation process, whereas 36 activate fibril formation. Several activators and inhibitors were subjected to further anal. using anal. ultracentrifugation and CD. Activators typically display a 1:10 peptide:detergent stoichiometry for maximal activation, whereas the inhibitors are effective at a 1:1 stoichiometry. Anal. ultracentrifugation and CD experiments show that activators promote a mixture of unfolded and β-sheet structures and rapidly form large aggregates, whereas inhibitors induce α-helical structures that form stable dimeric/trimeric oligomers. The results suggest that Aβ1-42 contains at least one small mol. binding site, which modulates the secondary structure and aggregation processes. Further studies of the binding of these compounds to Aβ may provide insight for developing therapeutic strategies aimed at stabilizing Aβ in a favorable conformation.
Journal of Biological Chemistry published new progress about 85618-21-9. 85618-21-9 belongs to alcohols-buliding-blocks, auxiliary class Tetrahydropyran,Chiral,sulfides,Alcohol, name is (2R,3S,4S,5R,6S)-2-(Hydroxymethyl)-6-(octylthio)tetrahydro-2H-pyran-3,4,5-triol, and the molecular formula is C14H28O5S, Application of (2R,3S,4S,5R,6S)-2-(Hydroxymethyl)-6-(octylthio)tetrahydro-2H-pyran-3,4,5-triol.
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