Poster abstracts
Poster number 96 submitted by Nisansala Muthunayake
Inhibitory effects of H69-targeting peptides on protein translation in bacteria
Nisansala Muthunayake (Chemistry, Wayne State University), Christine S. Chow (Chemistry, Wayne State University)
Abstract:
Identifying novel drug targets within the bacterial ribosome is an important approach to overcome the well-known problem of antibiotic resistance. The specific region of the ribosome under investigation in this study is helix 69 (H69). Considering the variety of functions of H69 in protein biosynthesis, as well as differences between the bacterial and human H69 sequences, this RNA is an attractive antibacterial drug target. In a previous study, short peptides that specifically bind to H69 were isolated by using phage-display libraries. The main objective of the current study was to investigate the inhibitory effects of these H69-targeting peptides on protein synthesis in bacteria. In order to determine their in vivo activity, minimum inhibitory experiments were carried out with E. coli MRE 600 and lpxA (lipid membrane mutant) strains. Our preliminary results showed inhibition of protein translation in the presence of peptides alone and in combination with other small molecules; however, it was clear that the peptides have cell penetration problems. Therefore, H69-targeting peptides were expressed in vivo as GFP-fusion proteins and their activities were monitored through cellular fluorescence levels. Expression of two different peptides was shown to have an inhibitory effect on bacterial cell growth. These findings will be helpful for future antimicrobial drug development.
Keywords: Ribosome, Helix 69, Peptides