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

Cory D. Rillahan, Erik Schwartz, Christoph Rademacher, Ryan McBride, Janani Rangarajan, Valery V. Fokin, James C. Paulson

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1417-1422
Number of pages6
JournalACS Chemical Biology
Volume8
Issue number7
DOIs
Publication statusPublished - 19 Jul 2013
Externally publishedYes

Fingerprint

Sialic Acid Binding Immunoglobulin-like Lectins
Libraries
Screening
Ligands
N-Acetylneuraminic Acid
Nanoparticles
Blood
Bearings (structural)
Printing
Alkynes
Immune system
Microarrays
Cell- and Tissue-Based Therapy
Computer Simulation
Immune System
Carrier Proteins
Leukocytes
Crystal structure
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Rillahan, C. D., Schwartz, E., Rademacher, C., McBride, R., Rangarajan, J., Fokin, V. V., & Paulson, J. C. (2013). On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7. ACS Chemical Biology, 8(7), 1417-1422. https://doi.org/10.1021/cb400125w

On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7. / Rillahan, Cory D.; Schwartz, Erik; Rademacher, Christoph; McBride, Ryan; Rangarajan, Janani; Fokin, Valery V.; Paulson, James C.

In: ACS Chemical Biology, Vol. 8, No. 7, 19.07.2013, p. 1417-1422.

Research output: Contribution to journalArticle

Rillahan, CD, Schwartz, E, Rademacher, C, McBride, R, Rangarajan, J, Fokin, VV & Paulson, JC 2013, 'On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7', ACS Chemical Biology, vol. 8, no. 7, pp. 1417-1422. https://doi.org/10.1021/cb400125w
Rillahan CD, Schwartz E, Rademacher C, McBride R, Rangarajan J, Fokin VV et al. On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7. ACS Chemical Biology. 2013 Jul 19;8(7):1417-1422. https://doi.org/10.1021/cb400125w
Rillahan, Cory D. ; Schwartz, Erik ; Rademacher, Christoph ; McBride, Ryan ; Rangarajan, Janani ; Fokin, Valery V. ; Paulson, James C. / On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7. In: ACS Chemical Biology. 2013 ; Vol. 8, No. 7. pp. 1417-1422.
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