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  • Structure-Based Development of Galectin- Specific Inhibitors

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    Bum-Erdene_02Thesis_2015.pdf (105.1Mb)
    Author(s)
    Bum-Erdene, KB
    Primary Supervisor
    Blanchard, Helen
    Other Supervisors
    Grice, Darren
    Year published
    2015
    Metadata
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    Abstract
    Galectins are a family of β-galactoside-specific lectins with sequence and structure conservation within their carbohydrate recognition domains. Galectins are found in a variety of species such as fungi, fish, birds and mammals. Furthermore, galectins are located in the nucleus, the cytoplasm and the extracellular matrix with their expression and localization regulated by the cell and its environment. Galectins are implicated in a number of disease states such as inflammation and cancer. Galectin-3 contributes to the progression of every step of cancer, from malignant transformation to angiogenesis, metastasis, immune evasion ...
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    Galectins are a family of β-galactoside-specific lectins with sequence and structure conservation within their carbohydrate recognition domains. Galectins are found in a variety of species such as fungi, fish, birds and mammals. Furthermore, galectins are located in the nucleus, the cytoplasm and the extracellular matrix with their expression and localization regulated by the cell and its environment. Galectins are implicated in a number of disease states such as inflammation and cancer. Galectin-3 contributes to the progression of every step of cancer, from malignant transformation to angiogenesis, metastasis, immune evasion and to drug resistance. In contrast, galectin-4 plays contradicting roles in different cancers, enhancing metastasis of liver and lung cancers but inhibiting metastasis in colon and pancreatic cancers. The development of high-affinity selective inhibitors of galectins to probe their functions and to treat diseases is a major goal within the galectin field. Inhibition of galectins have mostly focused on galectin-3 and galectin-1, as these are the most thorougly studied galectins with significant correlation to disease progression. Divergent strategies have been employed in the inhibition of these galectins including saccharide modification, glycodendrimers with multiple peripheral saccharides, large natural complex polysaccharides such as modified citrus pectin as well as the use of peptides and peptidomimetics. Non-saccharide small molecule inhibitors toward galectins are not yet available. Recent reports regarding the anti-cancer capacity of galectins, such as for galectin-4, have highlighted the need for selective inhibitors. A major challenge in developing selective galectin inhibitors has been the high conservation of the carbohydrate binding site among galectins.
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    Thesis Type
    Thesis (PhD Doctorate)
    Degree Program
    Doctor of Philosophy (PhD)
    School
    Institute for Glycomics
    DOI
    https://doi.org/10.25904/1912/81
    Copyright Statement
    The author owns the copyright in this thesis, unless stated otherwise.
    Item Access Status
    Public
    Subject
    Galectins
    β-galactoside-specific lectins
    Cancer
    Galectin-4
    Publication URI
    http://hdl.handle.net/10072/368150
    Collection
    • Theses - Higher Degree by Research

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