6,6'-Aryl trehalose analogs as potential Mincle ligands

Bioorg Med Chem. 2020 Jul 15;28(14):115564. doi: 10.1016/j.bmc.2020.115564. Epub 2020 May 31.

Abstract

6,6'-Aryl trehalose derivatives have been synthesized with a view towards identifying novel Th-17-inducing vaccine adjuvants based on the high affinity Mincle ligand Brartemicin. The initial structure-activity relationships of these novel trehalose-based compounds were investigated. All compounds have been evaluated for their ability to engage the Mincle receptor and induce a potential pro-Th17 cytokine profile from human peripheral blood mononuclear cells based on IL-6 production in human peripheral blood mononuclear cells. The preliminary biological characterization of the designed analogs presented in this paper should aid in the future design and testing of more affine ligands that may foster the discovery of novel adjuvants with improved pharmacological properties.

Keywords: Adjuvant; Brartemicin; Mincle; TH-17; Trehalose diester; Trehalose dimycolate; Tuberculosis; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Lectins, C-Type / metabolism*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Ligands
  • Molecular Structure
  • Receptors, Immunologic / metabolism*
  • Structure-Activity Relationship
  • Trehalose / analogs & derivatives
  • Trehalose / chemistry
  • Trehalose / pharmacology*

Substances

  • CLEC4D protein, human
  • Lectins, C-Type
  • Ligands
  • Receptors, Immunologic
  • Trehalose