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Design, synthesis, and screening of a library of peptidyl bis-boroxoles as low molecular weight receptors for complex oligosaccharides in neutral water: identification of a selective receptor for the tumour marker TF-antigen

  • Author / Creator
    Pal, Arnab
  • The ability of boronic acids to bind reversibly to simple carbohydrates in neutral water can be exploited to address the problem of cell-surface recognition. Recently, it has been shown that benzoboroxole can complex hexopyranosides under physiological conditions. These hemiboronate units were essential to the design of a small library of welldefined peptidyl-diboroxole receptors for complex oligosaccharides. The library was synthesized using a combinatorial solid-phase approach with the Irori® technology, and it was screened in a biochemical assay for the selective recognition of the T-antigen disaccharide, a cancer-associated cell-surface marker. A few high-affinity receptors of low micromolar IC50 were identified, and their binding behavior in neutral water was characterized using competition experiments and a systematic evaluation of analogues. These results suggest that low molecular weight receptors for biologically relevant glycoconjugates could be made to rival the efficiency of Nature’s carbohydratebinding proteins.

  • Subjects / Keywords
  • Graduation date
    2009-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3635N
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Chemistry
  • Supervisor / co-supervisor and their department(s)
    • Dr. Dennis G. Hall (Department of Chemistry)
  • Examining committee members and their departments
    • Dr. Todd L. Lowary (Department of Chemistry)
    • Dr. Mario F. Feldman (Department of Biological Sciences)