John H. Thurston, Ph.D.

Summary: The enzyme MTN (methylthioadenosine/S-adenosylhomocysteine nucleosidase) is bacterial specific and is responsible for the catabolism and salvage of growth-inhibitory nucleosides arising from polyamine synthesis and methylation biochemical pathways, among others.  Furthermore MTN has been shown to be integral in bacterial quorum sensing, a process of intercellular signaling that is used to govern population-wide behavior and phenotype expression (e.g. biofilm formation, virulence factors etc.).  Due to its absence in humans and its involvement in a wide array of microbial processes, MTN is an attractive target for drug development for antimicrobial applications.  Our project, which is being run collaboration with Dr. Ken Cornell’s lab at Boise State University, is focused on the design, synthesis and characterization of novel small molecule inhibitors of this enzyme.

Minimum Classes: Students must have completed General Chemistry I & II, with all associated labs and have at least one semester of organic chemistry and lab.  A full year of organic chemistry (with lab) is desirable.  Additional experience in the handling of air sensitive compounds and in the physical and spectroscopic characterization of small molecules will be very helpful.

Projects: The majority of the work associated with this project will be directed toward the design, synthesis and characterization of potential molecular inhibitors of MTN.  Additional studies including in vitro assays and in vivo assays of potential inhibitors will conducted to ascertain the efficacy of the drugs developed as part of this study.  Computer modeling studies may be employed to help direct and refine our synthetic efforts.