Date of Award

Spring 2019

Document Type

Open Access Dissertation

First Advisor

John J. Lavigne

Abstract

Cancer diagnostic tools have been pushed to the forefront of medical research because a person’s chance of survival is directly correlated with how early the tumor is identified and treatment is begun. In searching for the subtle differences between healthy and tumor cells, almost every type of cancer has been shown to under, over, or neo express glycans, and these changes in the glycan fingerprint can continue as the disease progresses. This provides a powerful diagnostic opportunity that’s works by screening for glycoproteins and glycosylation patterns that deviate from normal cells.

Boronic acids have a useful and tunable property in that they can selectively, but cross-reactively, bind to carbohydrates. They do so by forming reversible covalent bonds with 1,2 and 1,3 cis-diols, which are found all over saccharides. The Lavigne laboratory has created bead-based sensors, called Synthetic Lectins, which can preferentially bind to different glycoproteins in biological samples, using modified boronic acids bound to amino acids conjugated to polystyrene beads.

This dissertation will first cover instrumentation and procedural developments that have advanced this project, to allow it to be translated into the clinical setting. Following this will be a deeper analysis and validation of this glycoprotein sensor array, using hydropholic interaction liquid chromatography-electrospray ionization-mass spectrometry (HILIC-ESI-MS) to analyze N-linked glycans extracted from breast cell line secretions using the Synthetic Lectin array. Finally, new ways of using this Synthetic Lectin array as a prognostic tool and a research tool will be explored.

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