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

Результат исследований: Материалы для журналаСтатья

30 Цитирования (Scopus)

Аннотация

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.

Язык оригиналаАнглийский
Страницы (с-по)1417-1422
Число страниц6
ЖурналACS Chemical Biology
Том8
Номер выпуска7
DOI
СостояниеОпубликовано - 19 июл 2013
Опубликовано для внешнего пользованияДа

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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  • Цитировать

    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