Date of Graduation

Summer 5-18-2012

Document Type

Thesis

Degree Name

Master of Science (MS)

Department/Program

Chemistry

First Advisor

Megan E. Bolitho

Abstract

Quorum sensing (QS) is a process of bacterial cell-to-cell communication that conveys population density information in order to coordinate gene expression to produce synchronized behaviors. QS regulates the expression of virulence genes in many species of bacteria; hence, the manipulation of QS pathways may lead to treatment options against many bacterial diseases. The LuxS enzyme converts S-ribosyl-L-homocysteine (SRH) into homocysteine (HCys) and 4(S),5-dihydroxypentane-2,3-dione (DPD), which is the precursor of autoinducer-2 (AI-2). Thus, inhibitors of LuxS could prevent QS by halting the conversion of SRH to AI-2 rendering the cell “uncommunicative”. This work shows the successful chemical synthesis of SRH and progress towards the synthesis of SRH analogs substituted at the HCys C3-position. The chemically-synthesized SRH can be utilized as the substrate for LuxS inhibition assays. The “HCys-C3” SRH analogs are designed to prevent the conversion of SRH to AI-2 by blocking the necessary association between the two LuxS monomers. This work also provided inspiration for the design and synthesis of other kinds of SRH analogs that could also serve as LuxS inhibitors.

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