Steering Siglec-Sialic Acid Interactions on Living Cells using Bioorthogonal Chemistry

TY - JOUR

T1 - Steering Siglec-Sialic Acid Interactions on Living Cells using Bioorthogonal Chemistry

AU - Büll, Christian

AU - Heise, Torben

AU - van Hilten, Niek

AU - Pijnenborg, Johan F A

AU - Bloemendal, Victor R L J

AU - Gerrits, Lotte

AU - Kers-Rebel, Esther D

AU - Ritschel, Tina

AU - den Brok, Martijn H

AU - Adema, Gosse J

AU - Boltje, Thomas J

N1 - © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2017/3/13

Y1 - 2017/3/13

N2 - 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.

AB - 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.

U2 - 10.1002/anie.201612193

DO - 10.1002/anie.201612193

M3 - Journal article

C2 - 28194834

SN - 1433-7851

VL - 56

SP - 3309

EP - 3313

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 12

ER -