Steering Siglec-Sialic Acid Interactions on Living Cells using Bioorthogonal Chemistry
SourceAngewandte Chemie. International Edition, 56, 12, (2017), pp. 3309-3313
Article / Letter to editor
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Synthetic Organic Chemistry
Angewandte Chemie. International Edition
SubjectRadboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences; Synthetic Organic Chemistry
Sialic acid sugars that terminate cell-surface glycans form the ligands for the sialic acid binding immunoglobulin-like lectin (Siglec) family, which are immunomodulatory receptors expressed by immune cells. Interactions between sialic acid and Siglecs regulate the immune system, and aberrations contribute to pathologies like autoimmunity and cancer. Sialic acid/Siglec interactions between living cells are difficult to study owing to a lack of specific tools. Here, we report a glycoengineering approach to remodel the sialic acids of living cells and their binding to Siglecs. Using bioorthogonal chemistry, a library of cells with more than sixty different sialic acid modifications was generated that showed dramatically increased binding toward the different Siglec family members. Rational design reduced cross-reactivity and led to the discovery of three selective Siglec-5/14 ligands. Furthermore, glycoengineered cells carrying sialic acid ligands for Siglec-3 dampened the activation of Siglec-3+ monocytic cells through the NF-kappaB and IRF pathways.
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