New chemical linkage systems to address biological problems
Geoghan, Allison F.
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The research reported in this thesis explored and developed the formation of reversible and irreversible chemical linkages for use in biological systems. Through the synthesis of a variety of peptides and small molecules, a new ligand system was developed to form covalent linkages through the Cu-catalyzed azide-alkyne cycloaddition (CuAAC). Additionally, a class of ester-amide oxanorbornadiene (EA-OND) molecules was developed to release alcohol cargos by succinimide formation upon addition of a thiol reagent. The attachment and thiol-dependent release of cholesterol was characterized as an example of the manipulation of a drug-like cargo. Lastly, a new method for combating bacterial infections through the covalent attachment of antimicrobial small molecules to medical tubing via the CuAAC reaction was developed. These modifications minimized the number of viable bacteria attached to the surface of the material and were non-toxic to mammalian cells. Together, these projects expand the chemical toolbox for applying new technologies to biological systems.