Date of Award

6-10-2014

Document Type

Thesis

Publisher

Santa Clara University

First Advisor

Zhiwen Zhang

Abstract

At the intersection of bio-device engineering and bio-pharmaceutical studies, our project involved the design of a hydraulic manifold to be used in isothermal titration calorimetry (ITC), with the ultimate goal of using ITC to study the thermodynamic binding parameters of potential anti-Methicillin Resistant Staphylococcus aureus (MRSA) agents to our drug target, Sortase A. The hydraulic manifold redesign included the analysis of materials such as high density polyethylene (HDPE), polytetrafluorethylene (PTFE, ‘Teflon’), and polycarbonate as well as the implementation of a new construct of the manifold itself. Sortase A is a transpeptidase found in Gram-positive bacteria and catalyses the attachment of virulent surface proteins to the cell wall by recognizing a specific amino acid motif (LPXTG). The ability of the bacterium to communicate with and infect host cells is linked to the Sortase A mechanism. We have identified pyridostigmine bromide as the primary drug target based upon the analysis of ITC data.

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