Book of Abstracts: Albany 2007
June 19-23 2007
Discovery of Peptides that Target the Bacterial Decoding Region of 16S rRNA
Protein synthesis by the ribosome is an essential process in all cells. The decoding region (helix 44) of 16S ribosomal RNA (rRNA) of the small subunit is a very important functional region; it is involved in binding to mRNA, tRNAs, and the large subunit rRNA. The decoding region is involved in translational accuracy, such that proteins are synthesized essentially without errors. Some of the known antibiotics, such as aminoglycosides, bind to the decoding region. We used phage display to identify peptide sequences that potentially target this region, studied the binding of individual peptides to the ribosome and 16S rRNA, and examined the ability of selected peptides to inhibit ribosome function. There are three modified nucleosides in decoding region of E. coli 16S rRNA, namely 5-methylcytidine (m5C), 3-methyluridine (m3U), and N4, 2'-O-dimethylcytidine (m4Cm). The functional significance of these modified nucleosides is not completely understood. These modified nucleosides were synthesized, converted to the corresponding phosphoramidites, and incorporated into decoding region model RNAs. Biophysical studies were carried out to determine the significance of the modified nucleosides within the context of the decoding region, and to determine their effects on small molecule and peptide binding.
Dept of Chemistry