Butyrylcholinesterase (BuChE) is known to show increased activity in patients with Alzheimer’s Disease and likely contributes to the symptomatic decline in cognition. Therefore, it is an attractive goal to develop a synthetic drug that is highly specific for inhibiting BuChE. Herein, we build upon previous organophosphorus inhibitor designs by changing substituents on the phosphorus center in two ways: 1) the addition of substrate features to mimic the cationic-pi interaction, and 2) the substitution of oxygen for sulfur atoms to incorporate a better leaving group. However, for the former, stereochemistry on the phosphorus center was also evaluated for using enantiomerically enriched mixtures. Herein, the synthesis, purification, and biological characterization of a library of inhibitors are detailed. The results of these experiments increase our understanding of the molecular interactions between the potential drug candidate and its target and inform us on how to design more potent, target-specific drugs.
|Commitee:||Schwans, Jason, McAbee, Douglas|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 81/12(E), Masters Abstracts International|
|Subjects:||Biochemistry, Organic chemistry|
|Keywords:||Butyrylcholinesterase, Organophosphate, Sulfur substitution|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be