期刊
ACS CHEMICAL BIOLOGY
卷 8, 期 7, 页码 1417-1422出版社
AMER CHEMICAL SOC
DOI: 10.1021/cb400125w
关键词
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资金
- National Institutes of Health [P01HL107151, AI050143, T32AI007606, GM087620]
- Schering-Plough Research Institute postdoctoral Fellowship
- Rubicon fellowship from The Netherlands Organization For Scientific Research (NWO)
- Emmy Noether fellowship from the German Research Foundation [RA911/2-1]
- Max Planck Society
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL107151] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007606, R01AI050143] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM087620] Funding Source: NIH RePORTER
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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