Author

Karen Sanders

Date Approved

2010

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department or School

Chemistry

Committee Member

Cory Emal, PhD, Chair

Committee Member

Arthur Howard, PhD

Committee Member

Deborah Heyl-Clegg, PhD

Abstract

The inhibition of plasminogen activator inhibitor-1 (PAI-1) is anticipated to increase our understanding of various human ailments with which high levels of PAI-1 have been associated, including diabetes, stroke, and atherosclerosis. Previous accounts have reported the synthesis of inhibitors that bind to PAI-1 with a low affinity, inhibit the serpin plasma protein antithrombin III, and/or fail to inhibit PAI-1 when vitronectin, a cofactor of PAI-1 is present. The synthesis of small-molecule inhibitors of PAI-1 that improve upon these properties has been the main goal of this research. Research efforts focused on examining changes in inhibitor potency based on the manipulation of the inhibitors’ architecture, with particular attention paid to the number and positioning of multiple polyphenolic groups. The refinement of these synthesized moieties into selective and highly active species has been achieved.

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Chemistry Commons

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