Defense Date

2014

Document Type

Thesis

Degree Name

Master of Pharmaceutical Sciences

Department

Pharmaceutical Sciences

First Advisor

Glen E. Kellog

Abstract

Due to the development of multidrug resistance in Streptococcus pneumoniae, research has begun to define new drug targets for pneumonia therapy. Different research groups have identified a lipoprotein, PsaA that is important for pneumonia virulence. PsaA is a manganese transporter that is required for bacterial virulence and growth. We have employed computer modeling to virtually screen a small-molecule database for inhibition of PsaA function by targeting the metal binding pocket, performing receptor-based virtual screening and molecular docking and scoring to identify potential inhibitors of PsaA function. We have developed an assay for screening compounds, including the use of a PsaA mutant, testing of multiple compounds, and identification of compounds that inhibit Streptococcus pneumoniae growth at concentrations less than 20 μM. We experimentally tested the effect on Mn uptake and their PsaA dependence for 42 compounds, but these experiments suggested that these compounds were affecting bacterial growth by a different mechanism.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-19-2014

Available for download on Friday, August 16, 2024

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