Sialic Acid Mimetics to Target the Sialic Acid–Siglec Axis. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: Büll, Christian; Heise, Torben; Adema, Gosse J.; Boltje, Thomas J.
• Is Part Of: Trends in biochemical sciences. Volume 41:Issue 6(2016)
• Page Start: 519
• Page End: 531
• Publication Date: 2016-06
• Subjects: sialic acids -- sialic acid mimetics -- sialome -- Siglecs -- glycans -- glycoengineering; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2016.03.007
• Languages: English
• ISSNs: 0968-0004

Abstract

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. Trends: 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.