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Extracellular and intracellular small-molecule galectin-3 inhibitors

Author:
  • John Stegmayr
  • Fredrik Zetterberg
  • Michael C. Carlsson
  • Xiaoli Huang
  • Gunjan Sharma
  • Barbro Kahl-Knutson
  • Hans Schambye
  • Ulf J. Nilsson
  • Stina Oredsson
  • Hakon Leffler
Publishing year: 2019-02-18
Language: English
Publication/Series: Scientific Reports
Volume: 9
Issue: 1
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

Galectin-3 is a carbohydrate binding protein which has important roles in cancer and immunity. Potent galectin-3 inhibitors have been synthesized, for experimental purposes and potential clinical use. As galectin-3 is implicated in both intra- and extracellular activities, permeability of galectin-3 inhibitors is an important parameter determining biological effects. We compared the cellular uptake of galectin-3 inhibitors and their potency in the intracellular or extracellular space. The inhibitors differed in their polar surface area (PSA), but had similar affinities for galectin-3. Using a well-established permeability assay, we confirmed that the uptake was significantly higher for the inhibitor with the lowest PSA, as expected. To analyze intracellular activity of the inhibitors, we developed a novel assay based on galectin-3 accumulation around damaged intracellular vesicles. The results show striking differences between the inhibitors intracellular potency, correlating with their PSAs. To test extracellular activity of the inhibitors, we analyzed their potency to block binding of galectin-3 to cell surfaces. All inhibitors were equally able to block galectin-3 binding to cells and this was proportional to their affinity for galectin-3. These inhibitors may serve as useful tools in exploring biological roles of galectin-3 and may further our understanding of intracellular versus extracellular roles of galectin-3.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Lung Bioengineering and Regeneration
  • ISSN: 2045-2322
Stina Oredsson
E-mail: stina [dot] oredsson [at] biol [dot] lu [dot] se

Professor

Functional zoology

+46 46 222 94 97

B-C208

4

Principal investigator

LUCC - Lund University Cancer Centre

Research group

Animal Physiology

Projects

Cell proliferation

Doctoral students and postdocs

PhD Students, main supervisor

Wendy Soria Sotillo

PhD Students, assistant supervisor

Atena Malakpour Permlid