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Development of Chemoenzymatic Labeling Approaches for the Detection of Fucosylated Biomarkers

Citation

Chaubard, Jean-Luc (2016) Development of Chemoenzymatic Labeling Approaches for the Detection of Fucosylated Biomarkers. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9K35RN1. http://resolver.caltech.edu/CaltechTHESIS:05052016-123724002

Abstract

Protein fucosylation regulates a diverse set of physiological functions such as memory and learning, development, and disease pathogenesis. However, our current understanding of these processes is far behind that of other post-translational modifications, such as phosphorylation. This is, in part, due to the lack of tools available for the study of this important protein modification. To address this need, I have developed novel chemoenzymatic methods that enable the labeling and detection of unique forms of fucosylation, specifically fucose-α(1-2)-galactose (Fucα(1-2)Gal) and core fucose. Additionally, novel glycosyltransferase assays were developed in-house to aid in the future development of both new and existing chemoenzymatic approaches.

I have demonstrated that the approach to detect Fucα(1-2)Gal is highly selective for this disaccharide motif, detects a variety of complex glycans and glycoproteins, and can be used to profile the relative abundance of this motif on live cells, discriminating malignant from normal cells. I have also shown that the chemoenzymatic detection of core fucose exhibits superior specificity towards this glycan on a variety of complex N-glycans and when compared to current fucose-specific lectins. Further, the approach is amenable to detection of core fucosylated glycans from multiple biological settings, can be exploited as an antibody-conjugation method, and can be integrated into a diagnostic platform for the profiling of protein specific core fucosylation levels. These approaches represent new potential strategies for biomarker identification and expand the technologies available for understanding the role of these important fucosylated glycans in physiology and disease.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Chemoenzymatic Labeling, Fucose, Glycan Detection
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Hsieh-Wilson, Linda C.
Thesis Committee:
  • Tirrell, David A. (chair)
  • Barton, Jacqueline K.
  • Lester, Henry A.
  • Hsieh-Wilson, Linda C.
  • Heath, James R.
Defense Date:11 April 2016
Record Number:CaltechTHESIS:05052016-123724002
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:05052016-123724002
DOI:10.7907/Z9K35RN1
Related URLs:
URLURL TypeDescription
http://pubs.acs.org/doi/pdf/10.1021/ja211312uDOIArticle adapted for chapter 2
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9703
Collection:CaltechTHESIS
Deposited By: Jean-Luc Chaubard
Deposited On:08 Mar 2017 19:09
Last Modified:13 Sep 2017 18:19

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