Date of Award
2024
Document Type
Thesis
Degree Name
Bachelor of Science
Department
Chemistry
First Advisor
Dr. Christopher Shugrue
Abstract
Cleavable linkers have demonstrated great potential in various applications of medicinal organic chemistry, such as in modern therapeutic development. Linkers are stable compounds that cleave in specific conditions to release molecular cargo. We have developed cleavable linkers based on nucleophilic aromatic substitution reactions on sulfonamide and benzothiazole substrates in small molecule and in peptide studies. Sulfonamides, commonly with an electron-withdrawing group, reacted in high conversion of starting material to the sulfide product in small molecule studies, but was unable to successfully cleave the sulfonamide linker on peptide in mild conditions. Next, a benzothiazole sulfone substrate was analyzed and optimized in small molecule studies with the addition of an electron-withdrawing group. The benzothiazole sulfone was readily synthesized on peptide and complete cleavage could be performed in mild nucleophilic conditions. Future explorations include expanding the variety of peptide residues that are compatible with cleavage conditions.
Recommended Citation
Dalton, Abigail, "Exploration of Sulfonamides and Benzothiazoles as Peptide-Based Cleavable Linkers" (2024). Honors Theses. 1746.
https://scholarship.richmond.edu/honors-theses/1746