A galactoside-binding protein tricked into binding unnatural pyranose derivatives: 3-deoxy-3-methyl-gulosides selectively inhibit galectin-1

Research output: Contribution to journalArticle

Abstract

Galectins are a family of galactoside-recognizing proteins involved in different galectin-subtype-specific inflammatory and tumor-promoting processes, which motivates the development of inhibitors that are more selective galectin inhibitors than natural ligand fragments. Here, we describe the synthesis and evaluation of 3-C-methyl-gulopyranoside derivatives and their evaluation as galectin inhibitors. Methyl 3-deoxy-3-C-(hydroxymethyl)-β-d-gulopyranoside showed 7-fold better affinity for galectin-1 than the natural monosaccharide fragment analog methyl β-d-galactopyranoside, as well as a high selectivity over galectin-2, 3, 4, 7, 8, and 9. Derivatization of the 3-C-hydroxymethyl into amides gave gulosides with improved selectivities and affinities; methyl 3-deoxy-3-C-(methyl-2,3,4,5,6-pentafluorobenzamide)-β-d-gulopyranoside had Kd 700 µM for galectin-1, while not binding any other galectin.

Details

Authors
Organisations
External organisations
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology

Keywords

  • Benzamide, Fluorescence polarization, Galectin-1, Gulopyranosides, Selective
Original languageEnglish
Article number3786
JournalInternational Journal of Molecular Sciences
Volume20
Issue number15
Publication statusPublished - 2019 Aug 1
Publication categoryResearch
Peer-reviewedYes