Synthesis of Nanoencapsulated Aminoglycosides as Small-Molecule Gene Therapeutics

Student: Michael Cuccarese
Department: Chemistry
Advisor: George O’Doherty

Abstract

Aminoglycosides are a class of broad-spectrum antibiotics. Neomycin is the active ingredient in the topical antibiotic Neosporin and other aminoglycosides, such as Kanamycin and Gentamicin, are regularly used to treat life-threatening bacterial infections. The bad news is that aminoglycosides cause harm to the kidneys and ears, in many cases causing hearing loss. Also, aminoglycosides can only be administered intravenously, which is a significant disadvantage hurdle in patient compliance. The plan to address these issues is twofold: The first is to encapsulate existing aminoglycosides into nanoparticles. This will help shield the positive charge on the aminoglycoside and help it escape from the bloodstream and diffuse into cells. This should also skirt the tendency of kidneys to aggressively pump in the drug because it will be hidden inside the nanoparticle. The second is to make new aminoglycosides. Using de novo palladium-catalyzed glycosylation, aminoglycosides with a similar framework but different characteristics will be synthesized in hopes of finding a better analogue.