Asymmetrically Branched Precision Glycooligomers Targeting Langerin

Biomacromolecules. 2019 Nov 11;20(11):4088-4095. doi: 10.1021/acs.biomac.9b00906. Epub 2019 Oct 24.

Abstract

Asymmetrically branched precision glycooligomers are synthesized by solid-phase polymer synthesis for studying multivalent carbohydrate-protein interactions. Through the stepwise assembly of Fmoc-protected oligo(amidoamine) building blocks and Fmoc/Dde-protected lysine, straightforward variation of structural parameters such as the number and length of arms, as well as the number and position of carbohydrate ligands, is achieved. Binding of 1-arm and 3-arm glycooligomers toward lectin receptors langerin and concanavalin A (ConA) was evaluated where the smallest 3-arm glycooligomer shows the highest binding toward langerin, and stepwise elongation of one, two, or all three arms leads to decreased binding. When directly comparing binding toward langerin and ConA, we find that structural variation of the scaffold affects glycomimetic ligand binding differently for the different targets, indicating the potential to tune such ligands not only for their avidity but also for their selectivity toward different lectins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / chemistry*
  • Antigens, CD / genetics
  • Carbohydrates / chemical synthesis
  • Carbohydrates / chemistry*
  • Carbohydrates / genetics
  • Concanavalin A / chemistry
  • Concanavalin A / genetics
  • Concanavalin A / metabolism
  • Glycoproteins / chemical synthesis
  • Glycoproteins / chemistry*
  • Glycoproteins / ultrastructure
  • Humans
  • Lectins, C-Type / chemistry*
  • Lectins, C-Type / genetics
  • Ligands
  • Mannose-Binding Lectins / chemistry*
  • Mannose-Binding Lectins / genetics
  • Protein Binding / genetics
  • Protein Conformation
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / ultrastructure
  • Receptors, Mitogen / chemistry
  • Receptors, Mitogen / genetics

Substances

  • Antigens, CD
  • CD207 protein, human
  • Carbohydrates
  • Glycoproteins
  • Lectins, C-Type
  • Ligands
  • Mannose-Binding Lectins
  • Proteins
  • Receptors, Mitogen
  • Concanavalin A