Mannobioside biomimetics that trigger DC-SIGN binding selectivity

Area of Science:

• Carbohydrate chemistry
• Immunology
• Infectious diseases

Background:

• Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) and langerin are C-type lectins involved in pathogen recognition.
• Targeting these receptors offers a potential strategy for developing anti-infective agents.
• These lectins have counteracting effects during infections by certain pathogens.

Purpose of the Study:

• To investigate the development of selective DC-SIGN targeting agents.
• To explore the potential of multivalent sp2-iminosugar-containing mannobioside analogs as biomimetic ligands.
• To assess the selectivity of these analogs towards DC-SIGN over langerin.

Main Methods:

• Synthesis of multivalent sp2-iminosugar-containing mannobioside analogs.
• Evaluation of binding affinity and selectivity towards DC-SIGN and langerin.
• Utilizing the canonical binding mode of high-mannose oligosaccharide ligands.

Main Results:

• The synthesized mannobioside analogs demonstrated complete selectivity for DC-SIGN.
• These analogs effectively mimicked the binding of natural high-mannose oligosaccharide ligands.
• The compounds leveraged the canonical binding mode for selective receptor interaction.

Conclusions:

• Multivalent sp2-iminosugar mannobioside analogs can achieve exclusive DC-SIGN targeting.
• These findings support the development of DC-SIGN selective agents.
• The biomimetic approach offers a promising avenue for novel anti-infective therapies.