Date of Award
12-2025
Language
English
Document Type
Honors Thesis
Degree Name
Bachelor of Science
Department
Biological Science
Advisor/Committee Chair
Ting Wang
Major
Biology
Abstract
Myotonic Dystrophy type 1 (DM1) results from expanded CUG repeat RNA that sequesters MBNL proteins and disrupts alternative splicing. Small molecules that bind toxic repeat RNA and release MBNL proteins represent a promising therapeutic strategy. This thesis examines newly synthesized modified polycyclic compounds (MPCs) engineered to target CUG RNA with enhanced specificity and efficacy. Through Suzuki–Miyaura coupling and benzoquinone-mediated cyclization, MPC03 was synthesized and characterized by NMR and LC–MS.
The biological activity of these compounds was assessed in DM1 patient-derived myotubes and fibroblasts. MPC03 consistently produced dose-dependent rescue of multiple MBNL-regulated exons, restoring splicing patterns toward those observed in healthy controls. These findings highlight the importance of specific structural features in facilitating effective RNA binding and functional correction. The results identify MPC03-like scaffolds as promising leads for RNA-targeted therapeutics and inform further optimization of small-molecule approaches for DM1 treatment.
Recommended Citation
Azis, Xhesika, "Development of Novel Small Molecule Therapeutics for Myotonic Dystrophy" (2025). Biological Sciences. 109.
https://scholarsarchive.library.albany.edu/honorscollege_biology/109