Date of Award
Spring 2025
Language
English
Embargo Period
4-22-2025
Document Type
Master's Thesis
Degree Name
Master of Science (MS)
College/School/Department
Department of Chemistry
Program
Chemistry
First Advisor
Ting Wang
Committee Members
Ting Wang, Jia Sheng
Keywords
Small molecule, Photoswitch, RNA therapy, Myotonic Dystrophy
Subject Categories
Nucleic Acids, Nucleotides, and Nucleosides | Polycyclic Compounds
Abstract
RNA plays a critical role in many biological functions, such as normal cellular functions or disease-related processes. Regulating biological processes through RNA-based therapeutics can be employed by the reversible photoregulation of oligonucleotides. Azobenzene, a light-responsive compound that changes conformation when exposed to ultraviolet (UV) or visible light, is attached to cytidine phosphoramidite to be incorporated in a series of RNA oligonucleotides. The reversibility of the nucleoside and oligonucleotide is verified through UV melting point experiments. The modified oligonucleotide can change conformation upon light irradiation to stop reverse transcription (RT) in the presence of many different reverse transcriptase enzymes. This technique can be used to optically control RNA structures and functions for gene therapy by limiting off-target effects. A redshifted azobenzene could be explored for safer biological applications using longer wavelengths of light.
Myotonic Dystrophy Type 1 (DM1) is a genetic disorder caused by expanded CTG repeats in the DMPK gene, leading to the sequestration of Muscleblind-like (MBNL) protein. The sequestration of this protein disrupts RNA splicing. Small molecules are emerging as promising drug candidates specifically polycyclic compounds in recently approved FDA pharmaceuticals. In this study, the use of modified polycyclic compounds (MPCs) is being explored as a splicing modulator. The MPC targets the toxic CUG repeat-expanded RNA, thereby rescuing MBNL proteins and restoring correct RNA processing. The synthetic route, purification, and characterization in our symmetrical benzoxazole MPC is being studied for its possible solubility advantages in aqueous solutions.
License
This work is licensed under the University at Albany Standard Author Agreement.
Recommended Citation
Boyer, Savia, "Synthesis of Small Molecules as Therapeutic Candidates" (2025). Electronic Theses & Dissertations (2024 - present). 143.
https://scholarsarchive.library.albany.edu/etd/143
