Date of Award

Spring 2018

Thesis Type

Rollins Access Only

Degree Name

Honors Bachelor of Arts

Department

Chemistry

Sponsor

Dr. James Patrone

Committee Member

Dr. Jay Pieczynski

Committee Member

Dr. Kasandra Riley

Abstract

Melanin is a pigment that plays a crucial role in several biochemical processes, including protection, in nearly every class of organisms. The melanin biosynthesis pathway is regulated by the rate-limiting enzyme, tyrosinase and is responsible for skin pigmentation, enzymatic browning in foods, and crucial defense mechanisms in other organisms. Tyrosinase, although structurally different based on complexity of organism, has an active site that is highly conserved. It has a di-copper active site where each copper is coordinated by three histidine residues and bridged by a water molecule. This active site catalyzes both the reaction of L-tyrosine to L-dopa and L-dopa to dopaquinone. There is a strong incentive to finding inhibitors of tyrosinase because it has industrial applications in both the skin-whitening industry and agricultural preservatives. This study used fragment-based drug discovery to identify novel inhibitors of tyrosinase. The study optimized a direct assay that spectrophotometrically observed dopachrome formation at 470 nm. Six molecules were identified with IC50 values comparable or better to the known inhibitor kojic acid. Kinetic studies clarified the mechanism of action of the identified inhibitors. Future directions include a more rigorous kinetic analysis of proposed molecules and inhibitor treatment in melanoma cells to observe reduction of melanin production in vivo.

Available for download on Friday, May 08, 2020

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