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Bifunctional Reagents for Oxime Ligation

  • Author / Creator
    Dandapat, Arpan
  • Oxime ligation is an effective conjugation strategy for biomolecules and polymers in aqueous solution. The reaction is chemoselective, joining an aldehyde or ketone electrophile with an aminooxy nucleophile. The oxime linkage is thermally and hydrolytically stable under most biological conditions. The most common problem with oxime ligation is that the reaction rate is relatively slow at biological pH. Several groups have improved the rates of oxime ligation using organic catalysts, such as aniline. These catalysts are often more effective at low pH, and can substantially improve the rates of conjugation. In this thesis, we explore modified organic catalysts that contain an aniline nucleophile and an aminooxy nucleophile on the same scaffold. These compounds were designed to act as ligation reagents that could form an oxime linkage in the absence of an exogenous catalyst. We synthesized the ligation reagents, and measured their rate of reaction with benzaldehyde as a model substrate. We find that the ligation reagents can achieve as much as five-fold acceleration relative to the un-catalyzed reactions, and are between 2-3 fold faster than catalysis with aniline alone. We propose a rationale for these enhanced rates, and propose that these reagents could be used to improve protein bioconjugation strategies.

  • Subjects / Keywords
  • Graduation date
    2014-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3QN5ZN8S
  • 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)
    • Cairo, Christopher (Chemistry)
  • Examining committee members and their departments
    • Vederas, John (Chemistry)
    • Serpe, Michael (chemistry)