2008 Rustbelt RNA Meeting






Talk abstracts

Talk on Friday 05:30-05:50pm submitted by Anne-Cecile Duc

The use of peptides for novel antibiotic development against the bacterial ribosome

Anne-Cecile E. Duc (Department of Chemistry, Wayne State University), Mei Li (Department of Chemistry, Wayne State University), Christine S. Chow (Department of Chemistry, Wayne State University)

The increasing number of resistant bacteria to the existing antibiotic panoply is of great concern. Among these antibiotics, almost half interfere with the protein synthesis machinery, whose core is the ribosome. Within its two subunits, the ribosome harbors several sites targeted by antibiotics (1), one of them being the A site. The A site, located on helix 44 of the small subunit 16S rRNA, is universally responsible for decoding mRNA into protein. In our research, a peptide binding to a 27-nucleotide A-site rRNA model (2) was identified by phage display. The role played by each amino acid in the affinity and specificity of the binding to the A-site rRNA target was investigated by performing alanine screening, in which the variant peptides were studied using biophysical methods such as electrospray-ionization mass spectrometry, enzymatic footprinting, and circular dichroism. The insights gained regarding interactions of the variant peptides with the E. coli A-site rRNA will lead us to modify the peptide to enhance its affinity, specificity, and activity as a potential antibiotic.

(1) Steitz. T. A., On the structural basis of peptide-bond formation and antibiotic resistance from atomic structures of the large ribosomal subunit. FEBS Letters 2005, 579, (4), 955-958.
(2) Fourmy D., R. M. I., Blanchard S. C., Puglisi J. D., Structure of the A Site of Escherichia coli 16 S Ribosomal RNA Complexed with an Aminoglycoside Antibiotic. Science 1996, 274, (5291), 1367-1371.

Keywords: Ribosome, Antibiotic, Peptide