Sialic Acid Mimetics to Target the Sialic Acid-Siglec Axis

Christian Büll; Torben Heise; Gosse J Adema; Thomas J Boltje

doi:10.1016/j.tibs.2016.03.007

Sialic Acid Mimetics to Target the Sialic Acid-Siglec Axis

Trends Biochem Sci. 2016 Jun;41(6):519-531. doi: 10.1016/j.tibs.2016.03.007. Epub 2016 Apr 13.

Authors

Christian Büll¹, Torben Heise², Gosse J Adema³, Thomas J Boltje⁴

Affiliations

¹ Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 28, 6525 Nijmegen GA, The Netherlands.
² Cluster for Molecular Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 Nijmegen AJ, The Netherlands.
³ Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 28, 6525 Nijmegen GA, The Netherlands. Electronic address: Gosse.Adema@radboudumc.nl.
⁴ Cluster for Molecular Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 Nijmegen AJ, The Netherlands. Electronic address: T.Boltje@science.ru.nl.

PMID: 27085506
DOI: 10.1016/j.tibs.2016.03.007

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.

Keywords: Siglecs; glycans; glycoengineering; sialic acid mimetics; sialic acids; sialome.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Aging / immunology*
B-Lymphocytes / drug effects
B-Lymphocytes / immunology
B-Lymphocytes / pathology
Biomimetic Materials / chemistry
Biomimetic Materials / therapeutic use*
Carbohydrate Sequence
Drug Carriers
Gene Expression
Humans
Immune System Diseases / drug therapy*
Immune System Diseases / genetics
Immune System Diseases / immunology
Immune System Diseases / pathology
Immunologic Factors / chemistry
Immunologic Factors / therapeutic use*
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology
Killer Cells, Natural / pathology
Molecular Targeted Therapy
Myeloid Cells / drug effects
Myeloid Cells / immunology
Myeloid Cells / pathology
Nanoparticles / therapeutic use
Protein Binding
Sialic Acid Binding Immunoglobulin-like Lectins / antagonists & inhibitors
Sialic Acid Binding Immunoglobulin-like Lectins / genetics
Sialic Acid Binding Immunoglobulin-like Lectins / immunology*
Sialic Acids / antagonists & inhibitors
Sialic Acids / chemistry
Sialic Acids / immunology*
Sialyltransferases / antagonists & inhibitors
Sialyltransferases / genetics
Sialyltransferases / immunology
T-Lymphocytes / drug effects
T-Lymphocytes / immunology
T-Lymphocytes / pathology

Substances

Drug Carriers
Immunologic Factors
Sialic Acid Binding Immunoglobulin-like Lectins
Sialic Acids
Sialyltransferases