Development of the Engineered Biological Model Systems and Chemoselective Redox Responsive Ligation (CRRL) Public Deposited

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  • March 20, 2019
Creator
  • Park, Sungjin
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Biological model substrates were developed and engineered for cell adhesion and migration studies. The substrates are based on hydroquinone-presenting (HQ) self-assembled monolayers on gold surfaces that can be electrochemically activated for ligand immobilization. Combined with tetra(ethylene glycol)-terminated alkanethiol, the substrates secure biospecific interactions between cell adhesion receptors and ligands, as well as provide the ability to characterize the amount of immobilized ligand. In chapter 2, these model surfaces were used to study the biological role of decoupled PHSRN, found in the 9th type III domain of fibronectin when it is presented to Swiss 3T3 albino mouse fibroblasts. We found that PHSRN-integrin interactions enhanced lamellipodia protrusions by increasing Rac1 activity, which is associated with cross-talk between adhesion receptors and soluble factors. These novel biological model systems were further extended toward the development of a new platform based on reacting soluble ketone- or aldehyde-tethered ligands to surface-bound oxyamine-containing alkanethiols to generate a covalent oxime linkage to the surface in chapter 3. By photoprotecting the oxyamine group with nitroveratryloxycarbonyl chloride and then selectively deprotecting through microfiche film, bioligands and fibroblast cells could be immobilized in patterns and gradients. Expanding on the HQ platform in chapters 1 and 2, a general methodology to immobilize and release oxyamine ligands on an electroactive quinone monolayer by electrochemical reduction was reported in chapter 4. The HQ surface is catalytic, can perform several rounds of immobilization and release of ligands, and also converts the oxyamine functional group to a hydroxyl group by a mild electrochemical potential. In chapter 5, a general chemoselective redox responsive ligation and release strategy for molecular conjugation and cleavage was introduced. The HQ is converted to benzoquinone to form stable quinone oxime with oxyamine-tethered ligands that can be further cleaved by reduction, yielding aminophenol and hydroxyl-terminated ligand. The conjugation and cleavage reactions are controlled by mild chemical or electrochemical redox signals and can be performed at physiological conditions (pH 7.4, 37 oC) without the use of a catalyst.
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  • In Copyright
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  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry."
Advisor
  • Yousaf, Muhammad
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  • Chapel Hill, NC
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  • Open access
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