Poster abstracts
Poster number 34 submitted by Sarah Rundell
Structure-activity relationship of minimal bPNAs
Sarah Rundell (Chemistry and Biochemistry, Ohio State University), Shekariah Devari (Chemistry and Biochemistry, Ohio State University), Shiqin Miao (Chemistry and Biochemistry, Ohio State University)
Abstract:
Our lab utilizes bPNA+ which are α-PNAs with modified lysines bearing a melamine (M) base mimic (K2M) that can bind to 4 T/U bases. Our recent publications show the ability of our (SK2M)3 bPNA+ to bind to RNA modified to include two genetically-encoded U6 domains. We hypothesized that insights into the drivers of DNA/RNA binding could be obtained by structural variation and thermodynamic characterization of the DNA and RNA binding properties of a library of 4M bPNAs. A 4M bPNA library was prepared by SPPS that sampled different backbone topologies while maintaining overall charge, and subject to Van’t Hoff analysis. All of the derivatives had better binding to DNA (avg Tm = 40oC) than to RNA (avg Tm = 24°C). Tripeptide, dipeptide and diketopiperazine bPNA scaffolds were studied, with the DKP exhibiting the strongest DNA and RNA binding. Overall, we find that a wide range of variation may be tolerated within the tripeptide scaffold, while significant gains in binding are observed upon cyclic constraint of the bPNA backbone. .
Keywords: bPNA, DNARNA, melamine