Facile access to pseudo-thio-1,2-dimannoside, a new glycomimetic DC-SIGN antagonist

Bioorg Med Chem. 2017 Oct 1;25(19):5142-5147. doi: 10.1016/j.bmc.2017.03.046. Epub 2017 Mar 22.

Abstract

The synthesis and conformational analysis of pseudo-thio-1,2-dimannoside are described. This molecule mimics mannobioside (Manα(1,2)Man) and is an analog of pseudo-1,2-dimannoside, with expected increased stability to enzymatic hydrolysis. A short and efficient synthesis was developed based on an epoxide ring-opening reaction by a mannosyl thiolate, generated in situ from the corresponding thioacetate. NMR-NOESY studies supported by MM3∗ calculations showed that the pseudo-thio-1,2-dimannoside shares the conformational behavior of the pseudo-1,2-dimannoside and is a structural mimic of the natural disaccharide. Its affinity for DC-SIGN was measured by SPR and found to be comparable to the corresponding O-linked analog, offering good opportunities for further developments.

Keywords: DC-SIGN; Glycomimetics; Mannobioside; NOESY; Thioglycosides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion Molecules / antagonists & inhibitors*
  • Cell Adhesion Molecules / metabolism
  • Drug Design
  • Humans
  • Lectins, C-Type / antagonists & inhibitors*
  • Lectins, C-Type / metabolism
  • Mannosides / chemistry*
  • Mannosides / pharmacology*
  • Models, Molecular
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Cell Surface / metabolism
  • Surface Plasmon Resonance
  • Thioglycosides / chemistry
  • Thioglycosides / pharmacology

Substances

  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Mannosides
  • Receptors, Cell Surface
  • Thioglycosides