地 点：资环楼105 室（芭田报告厅）
报 告 人：陈刚 助理教授
报告题目：Targeting RNA sequences and structures with a
PNA-based programmable platform
主 持 人：刘定祥 教授
RNAs perform a diverse array of catalytic and regulatory functions in viruses and cells and are becoming increasingly important disease biomarkers and drug targets. RNA structures are mainly stabilized by base paired double-stranded (ds) stem regions. Together with single-stranded (ss) loop regions, RNAs can fold into complex secondary and tertiary structures, facilitating the molecular recognition of RNA structures by small molecules and peptides/proteins. Currently, programmable RNA structure-specific and tight-binding ligands are relatively unexplored. Peptide nucleic acid (PNA) is characterized by a neutral, peptide-like backbone, with superior chemical stability and strong binding to complementary RNA/DNA sequences. Importantly, PNAs conjugated with cell-penetrating moieties show promising bioactivities in animal models. In this presentation, I will present our results on the synthesis and biophysical characterization of the novel chemically-modified dsRNA-binding PNAs (dbPNAs), which show selective recognition of dsRNAs over ssRNAs and dsDNAs in a sequence-specific manner. dbPNAs and traditional antisense PNAs (asPNAs) can be combined to serve as useful dsRNA-ssRNA junction-specific molecular glues for the probing and targeting of many biologically and medically important RNA structures in transcriptomes. I will discuss the applications of the PNAs platform in targeting a miRNA hairpin precursor, a tau pre-mRNA splice site hairpin structure, and an influenza viral RNA structure.