Coding RNA has been studied extensively, yet comprises only 2% of transcribed DNA, leaving a vast amount of non-coding RNA underexplored. Peptide nucleic acids (PNAs) are synthetic nucleic acid mimics that allow for exploration of RNA structure and function. This project focuses on comparing the binding affinity of hydrogen bonding and pi-stacking interactions within nucleobase modified PNAs to target double-helical RNA sequences through triple helix formation. Forming this triple helical RNA structure involves the binding of synthesized PNA monomers to the Hoogsteen face of the RNA duplex. Synthesis of previous extended nucleobases involved the alkylation of isoorotic acid, followed by coupling to an amino-containing arene such as 3-amino-2-pyrazinecarboxamide, where the carboxamide provides a proposed third hydrogen bonding donor (Io4). In this project, Io4p, which lacks the carboxamide while retaining the aromatic pyrazine, was designed to determine the necessity of the third hydrogen bond. It is hypothesized that the Io4p PNA monomer will produce similar binding affinity to the Io4 PNA monomer, and once incorporated into PNA will be tested for RNA binding. Pi-stacking will be further explored using other electron-poor aromatic rings, allowing for potential stacking with electron-rich anilines.

Synthesis of modified isoorotic acid nucleobases to compare pi-stacking and hydrogen bonding interactions in PNA:RNA2 triple helix formation

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.