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  • Lactulose as a novel template for anticancer drug development targeting galectins

    Author(s)
    Kishor, Chandan
    Ross, Renee L
    Blanchard, Helen
    Griffith University Author(s)
    Kishor, Chandan
    Year published
    2018
    Metadata
    Show full item record
    Abstract
    Galectins are carbohydrate binding proteins (lectins), which characteristically bind β‐galactosides. Galectins play a role in tumour progression through involvement in proliferation, metastasis, angiogenesis, immune evasion and drug resistance. There is need for inhibitors (antagonists) that are specific for distinct galectins and that can interfere with galectin‐carbohydrate interactions during cancer progression. Here, we propose that lactulose, a non‐digestible galactose‐fructose disaccharide, presents a novel inhibitor scaffold for design of inhibitors against galectins. Thermodynamic evaluation displays binding affinity ...
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    Galectins are carbohydrate binding proteins (lectins), which characteristically bind β‐galactosides. Galectins play a role in tumour progression through involvement in proliferation, metastasis, angiogenesis, immune evasion and drug resistance. There is need for inhibitors (antagonists) that are specific for distinct galectins and that can interfere with galectin‐carbohydrate interactions during cancer progression. Here, we propose that lactulose, a non‐digestible galactose‐fructose disaccharide, presents a novel inhibitor scaffold for design of inhibitors against galectins. Thermodynamic evaluation displays binding affinity of lactulose against the galectin‐1 and galectin‐3 carbohydrate recognition domain (CRD). Crystal structures of galectin‐1 and galectin‐3 in complex with lactulose reveal for the first time the molecular basis of the galectin‐lactulose interactions. Molecular modelling was implemented to propose novel lactulose derivatives as potent anti‐cancer agents.
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    Journal Title
    Chemical Biology and Drug Design
    Volume
    92
    Issue
    4
    DOI
    https://doi.org/10.1111/cbdd.13348
    Subject
    Biochemistry and cell biology
    Biochemistry and cell biology not elsewhere classified
    Galectin-1
    Galectin-3
    Lactulose
    Structure-based inhibitor design
    X-ray crystallography
    Publication URI
    http://hdl.handle.net/10072/381720
    Collection
    • Journal articles

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