Submission Date

7-21-2023

Document Type

Paper- Restricted to Campus Access

Department

Chemistry

Second Department

Biochemistry & Molecular Biology

Faculty Mentor

Samantha Wilner

Comments

Presented during the 25th Annual Summer Fellows Symposium, July 21, 2023 at Ursinus College.

Project Description

Lipids, due to their amphipathic makeup, self-assemble into small, nearly identical vesicles called micelles. Because these micelles have a hydrophobic core, they can hold therapeutics that are hydrophobic in nature. Their stability decreases, however, at low concentrations and in the presence of other proteins, specifically, serum proteins found in the bloodstream. The potential to control the stability of these micelles using DNA allows for the use of oligonucleotide-lipid conjugate treatments. This project focuses on the characterization of 1-octadecanol (monoacyl C18) lipids conjugated to DNA sequences predicted to form G-quadruplex, double helix, or triple helix structures and their effect on stability. Monoacyl C18 lipids were first activated into lipid phosphoramidites. After this synthesis was confirmed using 31P-NMR, DNA was conjugated, and its formation was corroborated via reverse-phase high-performance liquid chromatography. Micelles made of these DNA-lipid conjugates were assembled via thin-film hydration, and their size was measured using dynamic light scattering. Micelle stability was tested using fluorescence resonance energy transfer. Critical micelle concentration was found using Nile Red. Using circular dichroism, DNA-DNA interactions were analyzed to confirm the formation of characteristic DNA structures upon micelle assembly. Preliminary results indicate that G-quadruplex structures give the micelle the most stability while triple helices confer the least amount of stabilization. Investigating micelle stability using oligonucleotide-lipid conjugates will aid in achieving the desired durations of cargo release for many different therapeutic strategies.

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