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

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

Author information

1
Departments of Cell and Molecular Biology, ‡Chemical Physiology, and §Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

Abstract

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.

PMID:
23597400
PMCID:
PMC3751994
DOI:
10.1021/cb400125w
[Indexed for MEDLINE]
Free PMC Article

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