Biology

Title

Modifying Amine Oxidases: Molecular Probes and High-Throughput Screening

Date of Award

2017

Degree Type

Thesis

Degree Name

Master of Science in Biochemistry & Molecular Biology

Department

Biology

Chief Instructor

Charles E. Jakobsche

Second Reader

Noel D. Lazo

Third Reader

Donald E. Spratt

Abstract

Amine oxidases are an essential and disease-relevant family of enzymes in the body. As the first of two overarching projects, a molecular probe was developed for flavin-dependent amine oxidases (Chapter 1). The flavin-dependent subfamily regulates crucial neurotransmitters including dopamine and epinephrine. Implicated in complex disorders such as depression, autism, and Parkinson's disease, a probe for the subfamily would enable the discovery of new life-improving drugs. Taking inspiration from known small molecular inhibitors, we designed and synthesized an activity-based probe, equipped with a propargylamine binding domain and a dinitrophenol readout domain. Using L-Amino Acid Oxidase as a model enzyme, a fluorescent-based activity assay was optimized, allowing measurement of inhibition.

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