Nitric Oxide, NO, is an important neurotransmitter and signaling molecule in almost every system of the human body. Its regulation is equally important as a dysfunction in regulation leads to pathophysiologic conditions and disease states. There are many ways that NO is regulated, but one of the more common methods is to regulate the enzyme that creates it, Nitric Oxide Synthases or NOS. Again, many ways to regulate this enzyme exist, but this work focuses on inhibition by an endogenous molecule produced via the normal process of protein degradation, Asymmetric Dimethyl Arginine or ADMA. Another enzyme in the body is responsible for metabolism of ADMA called Dimethylarginine Dimethylaminohydrolase or DDAH. By regulating the activity of DDAH, we can control concentrations of ADMA and therefore the inhibition of NOS, which in turn regulates the production of NO. It is the purpose of this project to create a probe that can be used in vivo for the DDAH enzyme family using organic synthesis to produce a product that, when effectively bound to the enzyme target, can also undergo a click chemistry reaction to tailor the utility of the probe itself. The Dixon Lab has designed such a molecule and the synthesis is what follows.
|Advisor:||Dixon, Robert P.|
|Commitee:||DeMayo, Christina, Luesse, Sarah, Shaw, Michael|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 58/01M(E), Masters Abstracts International|
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