Author

Sarah Burke

Date Approved

11-12-2015

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department or School

Chemistry

Committee Member

Cory Emal, Ph.D, Chair

Committee Member

Harriet Lindsay, Ph.D.

Committee Member

Gregg Wilmes, Ph.D.

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is a serpin protein whose function is to inhibit tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and hence, fibrinolysis. This inhibition leads to decreased plasminogen to plasmin conversion, which results in deleterious effects on the organism, such as blood clots. Elevated levels of PAI-1 are implicated in a variety of diseases and conditions. We have synthesized a variety of novel, small-molecule PAI-1 inhibitors in order to establish a structure-function relationship throughout the compounds. This goal was accomplished through an iterative process in which only one aspect of the molecule was altered at a time. Knowledge of this structure-function relationship will help to guide future endeavors in PAI-1 inhibitors, which will eventually lead to a decrease in symptoms of conditions such as atherosclerosis, diabetes, and cancer.

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