Catalytic Metallodrug Targeting of MMP-2 and MMP-9
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Date
2012-06
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The Ohio State University
Abstract
Metastasis is the fatal weapon for most cancer. Through access to the vascular and lymphatic systems, cancer is able to spread to vital organs throughout the body. This is made possible by the degradation of basement membranes and cleavage of the extracellular matrix. Matrix metalloproteinases are the enzymes that are responsible for both of the aforementioned tasks. Two matrix metalloproteinases, MMP-2 and MMP-9, are zinc dependent enzymes that have roles in tumor progression through their involvement with the degradation of the ECM. Specific enzymes such as these are viable anti-cancer targets. This thesis evaluates the use of a metallodrug, which consists of a metal binding motif, a linker, and a target recognition domain to target these enzymes. Carbonic anhydrase, a well-studied enzyme in the literature was used as a model to design the metallodrugs. The results of this project show that the metallodrug shows promise as a therapeutic against carbonic anhydrase, and through modification could be used to inhibit and inactivate matrix metalloproteinases as well.
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Keywords
catalytic metallodrug targeting, MMP-2, MMP-9