Poster abstracts
Poster number 50 submitted by Sherrell Haney
Improving cell permeability of a ribosome targeting peptide as a potential antibiotic
Sherrell K. Haney (Chemistry, Wayne State University), Mackenzie J. Olbrys (Chemistry, Wayne State University), Prabuddha Waduge (Chemistry, Wayne State University), Dr. Christine S. Chow (Chemistry, Wayne State University)
Abstract:
The development of bacterial resistance against currently available antibiotics is a major problem. Therefore, it is important to develop novel strategies to overcome the bacterial resistance. Towards this end, a previous in vitro selection study in our lab identified several peptides targeting a functionally important region of the bacterial ribosome, helix 31 (h31). Even though several in vitro studies have been conducted previously, it is important to examine the in vivo activity of the selected peptides. The poor cell permeability of these peptides is a major challenge. In this study, we are specifically focusing on the peptide TLWDLIP, and fusing a cell-penetrating peptide (CPP), which is expected to improve its ability to cross the cell membrane, particularly for bacterial species. The objective of our study is to chemically synthesize TLWDLIP-CPP fused peptides and investigate their in vivo inhibitory activity against E. coli. The overall goal of this study is to assess the effect of fusing a CPP to h31-targeting peptide, which is important in the development of peptide-based potential antibiotics. First, TLWDLIP and TLWDLIP+CPP were chemically synthesized using solid-phase peptide synthesis. Then, the synthesized peptides were purified by employing high-performance liquid chromatography (HPLC) and characterized using matrix-assisted laser desorption/ionization (MALDI). Next, the minimum inhibitory concentration (MIC) studies were carried out against E. coli using the broth dilution method. The short-term goal is to complete the MIC studies and to assess the effect of the CPP on TLWDLIP’s activity. The long-term goal is to find new drug target sites that may effectively combat antibiotic resistance.
Keywords: peptide, drug delivery