Poster abstracts

Poster number 68 submitted by Shu Zhou

Azasugar Affinity for T Box Antiterminator Model RNA: Potential new class of RNA ligands

Shu Zhou (Department of Chemistry and Biochemistry, Ohio University), Samira Telshow (Department of Chemistry and Mineralogy, Leipzig University, Germany), Dr. Jennifer V. Hines (Department of Chemistry and Biochemistry, Ohio University)

Abstract:
The T box genes, which are found in Gram-positive bacteria, contain a highly-conserved sequence of nucleotides known as the T box sequence. Expression of these genes is regulated by the interaction of uncharged cognate tRNA with the 5’ untranslated region of the mRNA during transcription. This interaction involves, in part, the base pairing of the tRNA accepter end with four bases of the antiterminator, which prevents the formation of an alternative terminator secondary structure and results in complete transcription of the gene. In an effort to investigate the potential for molecular modulation of this mechanism with exogenous small molecules a set of azasugar ligands were investigated. The azasugar class of ligands are poly-hydroxylated nitrogen heterocycles. These carbohydrate analogs can be protonated at physiological pH resulting in chemical characteristics similar to aminoglycosides. Given the ability of T box antiterminator model RNA to bind aminoglyocosides, it was hypothesized that the antiterminator may also bind azasugars. Enzymatic probing, circular dichroism and fluorescence-based ligand binding assays were conducted to investigate the affinity and RNA structural effects of azasugar ligands binding to wild-type and a reduced function variant antiterminator model RNA .

Keywords: T box tranascription antitermination, Ligand, Fluorescence