TY - JOUR
T1 - Sialic Acid Mimetics to Target the Sialic Acid-Siglec Axis
AU - Büll, Christian
AU - Heise, Torben
AU - Adema, Gosse J
AU - Boltje, Thomas J
N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Sialic acid sugars are vital regulators of the immune system through binding to immunosuppressive sialic acid-binding immunoglobulin-like lectin (Siglec) receptors on immune cells. Aberrant sialic acid-Siglec interactions are associated with an increasing number of pathologies including infection, autoimmunity, and cancer. Therefore, the sialic acid-Siglec axis is an emerging target to prevent or affect the course of several diseases. Chemical modifications of the natural sialic acid ligands have led to sialic acid mimetics (SAMs) with improved binding affinity and selectivity towards Siglecs. Recent progress in glycobiotechnology allows the presentation of these SAMs on nanoparticles, polymers, and living cells via bioorthogonal synthesis. These developments now enable the detailed study of the sialic acid-Siglec axis including its therapeutic potential as an immune modulator. Sialic acid sugars are emerging as important regulators of the immune system through binding to immunosuppressive sialic acid-binding immunoglobulin-like lectin (Siglec) receptors. Aberrant sialic acid-Siglec interactions are associated with multiple diseases like autoimmunity, infection, and cancer. Recent advances now enable the synthesis of chemically modified sialic acid mimetics with high Siglec binding affinity that can be coupled to nanoparticles, polymers, or surface glycoproteins and glycolipids of living cells. The potent immune modulatory properties of sialic acid mimetics provide a strong rationale for therapeutic targeting of the sialic acid-Siglec axis.
AB - Sialic acid sugars are vital regulators of the immune system through binding to immunosuppressive sialic acid-binding immunoglobulin-like lectin (Siglec) receptors on immune cells. Aberrant sialic acid-Siglec interactions are associated with an increasing number of pathologies including infection, autoimmunity, and cancer. Therefore, the sialic acid-Siglec axis is an emerging target to prevent or affect the course of several diseases. Chemical modifications of the natural sialic acid ligands have led to sialic acid mimetics (SAMs) with improved binding affinity and selectivity towards Siglecs. Recent progress in glycobiotechnology allows the presentation of these SAMs on nanoparticles, polymers, and living cells via bioorthogonal synthesis. These developments now enable the detailed study of the sialic acid-Siglec axis including its therapeutic potential as an immune modulator. Sialic acid sugars are emerging as important regulators of the immune system through binding to immunosuppressive sialic acid-binding immunoglobulin-like lectin (Siglec) receptors. Aberrant sialic acid-Siglec interactions are associated with multiple diseases like autoimmunity, infection, and cancer. Recent advances now enable the synthesis of chemically modified sialic acid mimetics with high Siglec binding affinity that can be coupled to nanoparticles, polymers, or surface glycoproteins and glycolipids of living cells. The potent immune modulatory properties of sialic acid mimetics provide a strong rationale for therapeutic targeting of the sialic acid-Siglec axis.
KW - Aging/immunology
KW - B-Lymphocytes/drug effects
KW - Biomimetic Materials/chemistry
KW - Carbohydrate Sequence
KW - Drug Carriers
KW - Gene Expression
KW - Humans
KW - Immune System Diseases/drug therapy
KW - Immunologic Factors/chemistry
KW - Killer Cells, Natural/drug effects
KW - Molecular Targeted Therapy
KW - Myeloid Cells/drug effects
KW - Nanoparticles/therapeutic use
KW - Protein Binding
KW - Sialic Acid Binding Immunoglobulin-like Lectins/antagonists & inhibitors
KW - Sialic Acids/antagonists & inhibitors
KW - Sialyltransferases/antagonists & inhibitors
KW - T-Lymphocytes/drug effects
U2 - 10.1016/j.tibs.2016.03.007
DO - 10.1016/j.tibs.2016.03.007
M3 - Review
C2 - 27085506
SN - 0968-0004
VL - 41
SP - 519
EP - 531
JO - Trends in Biochemical Sciences
JF - Trends in Biochemical Sciences
IS - 6
ER -
