Lactulose as a novel template for anticancer drug development targeting galectins
Author(s)
Kishor, Chandan
Ross, Renee L
Blanchard, Helen
Griffith University Author(s)
Year published
2018
Metadata
Show full item recordAbstract
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 ...
View more >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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View more >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
Subject
Biochemistry and cell biology
Biochemistry and cell biology not elsewhere classified
Galectin-1
Galectin-3
Lactulose
Structure-based inhibitor design
X-ray crystallography