Poster abstracts

Poster number 93 submitted by Amy Zimmerman

Structure-activity relationship studies of peptide affinities for T box antiterminator RNA

Amy Zimmerman (Department of Chemistry and Biochemistry, Ohio University), Monique Richter (Faculty for Chemistry and Mineralogy, Leipzig University), Jennifer V. Hines (Department of Chemistry and Biochemistry, Ohio University)

Abstract:
T box antiterminator riboswitch regulation is found primarily in Gram-positive bacteria and is a major regulatory mechanism for genes related to amino acid biosynthesis. The 5' untranslated region of these genes monitor and respond to the charging ratio of cognate tRNA. The ultimate objective of this project is to develop novel RNA-targeted medicinal agents through examination of the structure and function of the RNA and associated ligands. A more specific aim is to find peptides that are capable of binding to the antiterminator of the Bacillus subtilis tyrS sequence to disrupt the tRNA-antiterminator complex critical for the functioning of the T box riboswitch. The antiterminator contains the highly conserved T box sequence and a seven nucleotide bulge, of which the first four nucleotides base pair with the tRNA in the complex. The model antiterminator, AM1A, contains the same T box sequence and seven nucleotide bulge and is used in binding studies with various peptide sequences. The goal is to find peptides that will bind well with the antiterminator and then place the ligand complex in further testing to identify the effect of the binding on the tRNA-antiterminator interaction. Fluorescence spectroscopy was used to determine two trends: first, the relative binding affinities of a small library of peptides to the AM1A and second, the effect of the relative position of the amino acids within the peptide on the relative binding affinity.

Keywords: Structure-activity relationship, peptide binding, RNA