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 language | English |
|---|---|
| Pages (from-to) | 1417-1422 |
| Number of pages | 6 |
| Journal | ACS Chemical Biology |
| Volume | 8 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 19 Jul 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7
AU - Rillahan, Cory D.
AU - Schwartz, Erik
AU - Rademacher, Christoph
AU - McBride, Ryan
AU - Rangarajan, Janani
AU - Fokin, Valery V.
AU - Paulson, James C.
PY - 2013/7/19
Y1 - 2013/7/19
N2 - 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.
AB - 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.
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U2 - 10.1021/cb400125w
DO - 10.1021/cb400125w
M3 - Article
VL - 8
SP - 1417
EP - 1422
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 7
ER -