Exceptional New Reagents for Bioconjugation

1 online resource (151 pages) : PDF

2016

University of North Carolina at Charlotte

At about the turn of this century the term "click" chemistry came into the common vernacular amongst chemists. "Click" is used to describe reactions that are "spring-loaded" and proceed well in a predictable manner, with no offensive byproduct and are soluble in innocuous solvents. In the chemical world it draws to mind the biosynthesis of a peptide or DNA. The prototypical example of this for the synthetic chemist is the 1,3-dipolar cycloaddition reaction of an azide with an alkyne. This project has entailed the synthesis of a new platform for bioconjugation reagents based upon isatoic anhydride. These new reagents meet the criteria originally suggested for click reagents: They react quickly and predictably with amines, such as those found on lysine residues, to form amides. They have an inoffensive byproduct (CO2) upon conjugation. They are soluble in innocuous solvents including water. They also have an additional very desirable property; they add a chromophore and a fluorophore to the conjugate and therefore are traceable. Click reactions have become a principle tool in bioconjugation, the process of introducing chemical functionality into biomolecules through a covalent bond. Click reactions offer a way of selectively incorporating functionality into biomolecules despite the presence of a large number of functional groups. These new reagents allow for conjugation via lysine residues. The applicability of this platform has been demonstrated through the construction of new antibody-drug conjugates, a growing class therapeutics used in the treatment of multiple types of cancer that allow for targeted drug delivery.

masters theses

Chemistry
Biochemistry

M.S.

Antibody-Drug Conjugate
Bioconjugation
Isatoic Anhydride

Chemistry

Ogle, Craig

Etzkorn, Markus
Troutman, Jerry
Dréau, Didier

Thesis (M.S.)--University of North Carolina at Charlotte, 2016.

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Garmon_uncc_0694N_11180

http://hdl.handle.net/20.500.13093/etd:113