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

Research output: Contribution to journalArticle

Abstract

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.

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Authors
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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
  • Immunology in the medical area

Keywords

  • Galactose, Inhibition, Triazole, Galectin, Azide
Original languageEnglish
Pages (from-to)5367-5378
JournalBioorganic & Medicinal Chemistry
Volume18
Issue number14
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Organic chemistry (S/LTH) (011001240)