Bioorganic, Medicinal

Microarrays to Discover New Antibiotics and to Study Interactions at Cell Surfaces

Microarrays have proven to be a versatile platform for studying a variety of cellular processes. For example, gene arrays can determine the expression levels of protein within a cell, and small molecule arrays facilitate the discovery of organic ligands that modulate the activity of a protein. Our group is interested in expanding the use of microarrays to make it a general platform to interrogate biological processes. Towards this end, we have developed array-based platforms to study interactions at cell surfaces, to study ligand-cell interactions, and to detect bacteria within complex mixtures of cells. We have also used microarrays to study the interactions of antibiotics to both therapeutic targets and resistance-causing enzymes. By studying the binding of resistance enzymes to a library of antibiotics we identified several inhibitors of antibiotic resistance-causing enzymes and new antibiotics that evaded resistance. Since the arrays require minute amounts of material to complete a screen (femto- to picomoles), we are using this powerful technique to rapidly deconvolute combinatorial libraries to find compounds that solve complex problems in molecular recognition. Research projects in our group use a variety of techniques ranging from organic synthesis of new antibiotics and biophysical techniques to measure the energetics of antibiotics binding to therapeutic targets and resistance enzymes.