Alzheimer’s Disease (AD) is described as a progressive disease that worsens cognitive function. The disease is associated with decreasing amounts of acetylcholine, rising levels of butyrylcholinesterase (BuChE) activity, and formation of β-amyloid (Aβ) plaques in the brain. Therefore, BuChE is considered a therapeutic target for improving symptoms of AD. Three bisphosphates were tested and were shown to be inhibitory and selective for BuChE. Of the three bisphosphates, tetrabutyl hexyl bisphosphate (TBH) is shown to be the most potent inhibitor of BuChE. Changes in secondary structure of BuChE were not observed in circular dichroism (CD) experiments upon binding of the bisphosphates. Through tryptophan fluorescence, one of the bisphosphates, tetraphenyl hexyl bisphosphate (TPH), showed subtle changes in the microenvironment of BuChE when bound to it in comparison to unbound BuChE. TBH is also shown to inhibit Aβ peptide aggregation in vitro. From these results, these bisphosphates are suggested to be potential therapeutics for treating AD.
|Commitee:||Bhandari, Deepali, Schwans, Jason|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 57/01M(E), Masters Abstracts International|
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