C-4 Modified Sialosides Enhance Binding to Siglec-2 (CD22): Towards Potent Siglec Inhibitors for Immunoglycotherapy

C-4 Modified Sialosides Enhance Binding to Siglec-2 (CD22): Towards Potent Siglec Inhibitors for Immunoglycotherapy

Two changes for the better: A novel class of sialic acid derivatives is prepared by modifying both the C‐4 and C‐9 positions of Neu5Aα2Me (see structure). This approach gives a lead compound that has sub‐micromolar affinity for Siglec‐2 and may provide a pathway for immunoglycotherapy strategies for...

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Veröffentlicht in:Angewandte Chemie International Edition 2013-03, Vol.52 (13), p.3616-3620
Hauptverfasser: Kelm, Sørge, Madge, Paul, Islam, Tasneem, Bennett, Ryan, Koliwer-Brandl, Hendrik, Waespy, Mario, von Itzstein, Mark, Haselhorst, Thomas
Format: Artikel
Sprache:eng
Schlagworte:
Affinity
Antigens, CD - metabolism
Antineoplastic Agents - therapeutic use
antitumor agents
Autoimmune diseases
Autoimmune Diseases - therapy
Binding
Derivatives
Humans
immunoglycotherapy
Immunotherapy
Inhibitors
Lead compounds
Lymphoma, B-Cell - therapy
Magnetic Resonance Spectroscopy
Myelin-Associated Glycoprotein - antagonists & inhibitors
Myelin-Associated Glycoprotein - metabolism
NMR spectroscopy
Pathways
Protein Binding
sialic acid
Sialic Acid Binding Ig-like Lectin 2 - antagonists & inhibitors
Sialic Acid Binding Ig-like Lectin 2 - metabolism
Sialic Acid Binding Immunoglobulin-like Lectins - antagonists & inhibitors
Sialic Acid Binding Immunoglobulin-like Lectins - metabolism
Sialic Acids - chemistry
Sialic Acids - metabolism
siglecs
Strategy
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Beschreibung
Zusammenfassung:Two changes for the better: A novel class of sialic acid derivatives is prepared by modifying both the C‐4 and C‐9 positions of Neu5Aα2Me (see structure). This approach gives a lead compound that has sub‐micromolar affinity for Siglec‐2 and may provide a pathway for immunoglycotherapy strategies for autoimmune diseases and B cell derived non‐Hodgkin's lymphoma.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201207267