1193784-40-5Relevant academic research and scientific papers
Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition
Delaine, Tamara,Collins, Patrick,MacKinnon, Alison,Sharma,Stegmayr, John,Rajput, Vishal K.,Mandal, Santanu,Cumpstey, Ian,Larumbe, Amaia,Salameh, Bader A.,Kahl-Knutsson, Barbro,van Hattum, Hilde,van Scherpenzeel, Monique,Pieters, Roland J.,Sethi, Tariq,Schambye, Hans,Oredsson, Stina,Leffler, Hakon,Blanchard, Helen,Nilsson, Ulf J.
, p. 1759 - 1770 (2016/11/17)
Discovery of glycan-competitive galectin-3-binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin-3 accumulation at damaged vesicles, hence revealing galectin-3–glycan interactions involved in fibrosis progression and in intracellular galectin-3 activities, is reported. 3,3′-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and -8 N-terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying low-nanomolar affinities for galectins-1 and -3 were identified in a competitive fluorescence anisotropy assay. X-ray structural analysis of selected compounds in complex with galectin-3, together with galectin-3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin-3. The most potent galectin-3 antagonist was demonstrated to act in an assay monitoring galectin-3 accumulation upon amitriptyline-induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin–carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone.
NOVEL SYNTHESIS OF GALACTOSIDE INHIBITORS
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Page/Page column 22-23, (2009/12/23)
The present invention relates to novel synthesis routes for preparation of thiodigalactosides of the general formula (12). The method comprises the use of a 3-azido-galactosyl thiouronium salt derivative, which is activated to the corresponding thiol in s
