Abstract
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.
| Original language | English |
|---|---|
| Journal | Trends in Biochemical Sciences |
| Volume | 41 |
| Issue number | 6 |
| Pages (from-to) | 519-531 |
| Number of pages | 13 |
| ISSN | 0968-0004 |
| DOIs | |
| Publication status | Published - 1 Jun 2016 |
| Externally published | Yes |
Keywords
- Aging/immunology
- B-Lymphocytes/drug effects
- Biomimetic Materials/chemistry
- Carbohydrate Sequence
- Drug Carriers
- Gene Expression
- Humans
- Immune System Diseases/drug therapy
- Immunologic Factors/chemistry
- Killer Cells, Natural/drug effects
- Molecular Targeted Therapy
- Myeloid Cells/drug effects
- Nanoparticles/therapeutic use
- Protein Binding
- Sialic Acid Binding Immunoglobulin-like Lectins/antagonists & inhibitors
- Sialic Acids/antagonists & inhibitors
- Sialyltransferases/antagonists & inhibitors
- T-Lymphocytes/drug effects
