1H-1,2,3-Triazol-1-yl thiodigalactoside derivatives as high affinity galectin-3 inhibitors

Summary, in English

Galactose C3-triazole derivatives were synthesized by Cu(I)-catalyzed cycloaddition between acetylenes and galactose C3-azido derivatives. Evaluation against galectin-3, 7, 8N (N-terminal) and 9N (N-terminal) revealed 1,4-disubstituted triazoles to be high-affinity inhibitors of galectin-3 with selectivity over galectin-7, 8N, and 9N. Conformational analysis of 1,4-di-and 1,4,5-tri-substituted galactose C3-triazoles suggested that a triazole C5-substituent interfered sterically with the galectin proteins, which explained their poor affinities compared to the corresponding 1,4-disubstituted triazoles. Introduction of two 1,4-disubstituted triazole moieties onto thiodigalactoside resulted in affinities down to 29 nM for galectin-3. (C) 2010 Elsevier Ltd. All rights reserved.

• Författare: Bader A. Salameh; Ian Cumpstey; Anders Sundin; Hakon Leffler; Ulf Nilsson
• Avdelning/ar: Centrum för analys och syntes; Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG
• Publiceringsår: 2010
• Språk: Engelska
• Sidor: 5367-5378
• Publikation/Tidskrift/Serie: Bioorganic & Medicinal Chemistry
• Volym: 18
• Issue: 14
• Länkar: http://dx.doi.org/10.1016/j.bmc.2010.05.040
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Microbiology in the medical area; Immunology in the medical area
• Nyckelord: Galactose; Inhibition; Triazole; Galectin; Azide
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0968-0896