DOI
https://doi.org/10.25772/KT8A-EV41
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