Epimers Switch Galectin-9 Domain Selectivity: 3 N-Aryl Galactosides Bind the C-Terminal and Gulosides Bind the N-Terminal

Research output: Contribution to journalArticle

Abstract

A series of 3-deoxy-3-N-arylated-β-d-galactoside and -guloside derivatives have been synthesized by cesium fluoride/trimetylsilylaryl triflate-mediated benzyne generation and N-arylation of 3-deoxy-3-amino-β-d-galactosides and -gulosides, respectively. Evaluation as ligands to galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9C, and 9N revealed that the galactosides selectively bound galectin-9C, whereas the gulosides selectively bound galectin-9N. Hence, the N-aryl group induces galectin-9 selectivity and the ligand 3C-configuration acts as an epimeric selectivity switch between the two domains of galectin-9. Furthermore, MD simulations revealed that galacto derivatives in galectin-9C and gulo derivatives in galectin-9N find stable poses with specific interactions, which proposes a possible explanation to the gal/gulo 9C/9N selectivity.

Details

Authors
Organisations
External organisations
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry

Keywords

  • epimers, Galactose, galectin-9, gulose, N-phenyl, selectivity
Original languageEnglish
Pages (from-to)34-39
JournalACS Medicinal Chemistry Letters
Volume11
Issue number1
Early online date2019 Dec 4
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes