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Identification of Fucose-α(1-2)-Galactose Binding Proteins in the Mammalian Brain

Citation

Wibowo, Arif (2013) Identification of Fucose-α(1-2)-Galactose Binding Proteins in the Mammalian Brain. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ETC4-N802. https://resolver.caltech.edu/CaltechTHESIS:06012013-114632816

Abstract

Fucose-α(1-2)-galactose (Fucα(1-2)Gal) carbohydrates have been implicated in cognitive functions. However, the underlying molecular mechanisms that govern these processes are not well understood. While significant progress has been made toward identifying glycoconjugates bearing this carbohydrate epitope, a major challenge remains the discovery of interactions mediated by these sugars. Here, we employ the use of multivalent glycopolymers to enable the proteomic identification of weak affinity, low abundant Fucα(1-2)Gal-binding proteins (i.e. lectins) from the brain. End-biotinylated glycopolymers containing photoactivatable crosslinkers were used to capture and enrich potential Fucα(1-2)Gal-specific lectins from rat brain lysates. Candidate lectins were tested for their ability to bind Fucα(1-2)Gal, and the functional significance of the interaction was investigated for one such candidate, SV2a, using a knock-out mouse system. Our results suggest an important role for this glycan-lectin interaction in facilitating synaptic changes necessary for neuronal communication. This study highlights the use of glycopolymer mimetics to discover novel lectins and identify functional interactions between fucosyl carbohydrates and lectins in the brain.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Lectin, Glycobiology, Proteomics, Polymer, Synaptic Vesicle
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Hsieh-Wilson, Linda C.
Thesis Committee:
  • Dervan, Peter B. (chair)
  • Beauchamp, Jesse L.
  • Grubbs, Robert H.
  • Hsieh-Wilson, Linda C.
Defense Date:30 May 2013
Funders:
Funding AgencyGrant Number
Howard Hughes Medical InstituteUNSPECIFIED
NIHR01 GMB84724
Record Number:CaltechTHESIS:06012013-114632816
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:06012013-114632816
DOI:10.7907/ETC4-N802
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7816
Collection:CaltechTHESIS
Deposited By: Arif Wibowo
Deposited On:29 Aug 2014 18:24
Last Modified:04 Oct 2019 00:01

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