Christiane Chbib (Larkin U):

Synthesis and biological evaluation of S-ribosylhomocysteine analogues as new antibacterials

Cell to cell communication in bacteria, otherwise known as quorum sensing (QS) is accomplished through the exchange of extracellular signaling molecules, among them is autoinducer-2 (AI-2). AI-2 is known to be universal since it is found in both Gram positive and negative bacteria. By interfering with the QS process, it may be possible to alter the course of a bacterium’s ability to harm humans and animals by causing infections.

We propose the design and synthesis of analogues of S-ribosylhomocysteine lacking the enolizable hydroxyl group at C2 to compete with the natural substrate for the LuxS enzyme. The alteration in the analogue structure should be able to obstruct the LuxS-catalyzed pathway by preventing the formation of the AI-2. By competitively inhibiting SRH interaction with LuxS and consequently inhibiting AI-2 synthesis, we are proposing a new mechanism of antibacterial action affecting the QS process in both Gram positive and negative bacteria.