On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7

ACS Chem Biol. 2013 Jul 19;8(7):1417-22. doi: 10.1021/cb400125w. Epub 2013 Apr 24.


The Siglec family of sialic acid-binding proteins are differentially expressed on white blood cells of the immune system and represent an attractive class of targets for cell-directed therapy. Nanoparticles decorated with high-affinity Siglec ligands show promise for delivering cargo to Siglec-bearing cells, but this approach has been limited by a lack of ligands with suitable affinity and selectivity. Building on previous work employing solution-phase sialoside library synthesis and subsequent microarray screening, we herein report a more streamlined 'on-chip' synthetic approach. By printing a small library of alkyne sialosides and subjecting these to 'on-chip' click reactions, the largest sialoside analogue library to date was generated. Siglec-screening identified a selective Siglec-7 ligand, which when displayed on liposomal nanoparticles, allows for targeting of Siglec-7(+) cells in peripheral human blood. In silico docking to the crystal structure of Siglec-7 provides a rationale for the affinity gains observed for this novel sialic acid analogue.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation, Myelomonocytic / chemistry*
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Delivery Systems
  • Drug Evaluation, Preclinical*
  • Fluoresceins / chemistry*
  • Humans
  • Jurkat Cells
  • Lectins / chemistry*
  • Lectins / metabolism
  • Ligands
  • Liposomes / chemistry
  • Microarray Analysis
  • Molecular Structure
  • Sialic Acids / chemistry*
  • Small Molecule Libraries / chemistry*


  • Antigens, Differentiation, Myelomonocytic
  • Fluoresceins
  • Lectins
  • Ligands
  • Liposomes
  • SIGLEC7 protein, human
  • Sialic Acids
  • Small Molecule Libraries