Steering Siglec–Sialic Acid Interactions on Living Cells using Bioorthogonal Chemistry. (14th February 2017)

• Record Type: Journal Article
• Authors: Büll, Christian; Heise, Torben; van Hilten, Niek; Pijnenborg, Johan F. A.; Bloemendal, Victor R. L. J.; Gerrits, Lotte; Kers‐Rebel, Esther D.; Ritschel, Tina; den Brok, Martijn H.; Adema, Gosse J.; Boltje, Thomas J.
• Is Part Of: Angewandte Chemie. Volume 129:Number 12(2017)
• Page Start: 3357
• Page End: 3361
• Publication Date: 2017-02-14
• Subjects: Bioorthogonale Chemie -- Immunologie -- Molecular Modeling -- Sialinsäuren -- Siglecs; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201612193
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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‐κB and IRF pathways.